Scharl, Michael; Barthel, Christiane; Rogler, Gerhard
During their disease course, the majority of Crohn's disease patients will develop a complicated disease which is characterized by the occurrence of fistulas and/or stenosis. Symptomatic, perianal fistulas should be surgically drained before anti-inflammatory therapy will be initiated. Antibiotics, such as metronidazole, improve disease symptomatic however, they are not sufficient to induce continuous fistula closure. For this purpose, azathioprine/6-mercaptopurine as well as anti-TNF antibodies are useful when administered continuously. Surgical options include seton drainage, fistula excision, fistula plugs and mucosa flaps. As ultima ratio, temporary ileostomy and proctectomy are to be discussed. Non-perianal fistulas often require surgical approaches. Symptomatic strictures or stenosis can be treated by anti-inflammatory medications (only if they are cause by inflammation), endoscopic balloon dilatation or surgery.
Mazziotti, Silvio; Blandino, Alfredo; Scribano, Emanuele; Gaeta, Michele; Mileto, Achille; Fries, Walter; Bombaci, Francesco; Ascenti, Giorgio
MR of the small bowel is a useful technique for the evaluation of both intraluminal and extraluminal pathologic involvement of the small bowel in patients with Crohn's disease. Crohn's disease is associated with a range of extraintestinal complications that sometimes may be the initial presenting symptoms. Some of these extraintestinal complications may not correlate with disease activity, but in general, they tend to follow the clinical course of disease and may have a high impact on life quality, morbidity, and even mortality in these patients. Our purpose is to describe some abdominopelvic extraintestinal complications of Crohn's disease, such as hepatopancreatobiliary, genitourinary, musculoskeletal, peritoneal, and lymph-nodal, detectable at MR enterography. Copyright © 2012 Wiley Periodicals, Inc.
Tian, Li; Tang, Anliu; Liu, Fen; Guo, Qin; Wang, Xiaoyan; Shen, Shourong
Crohn's disease (CD) is a nonspecific chronic intestinal inflammatory disease with unknown etiology. The course of CD is persistent and recurrent. In the progress, CD can come with many complications such as obstruction, fistula formation, perforation, and hemorrhage. The early diagnosis, treatment, and the time of the surgery for CD pose a big controversy and challenge. There was a female patient diagnosed as Crohn's disease with severe complication in department of Gastroenterology of the Third Xiangya Hospital, Central South University. We reported the diagnosis and treatment on this patient. The choice for the medicine and surgury was discussed.
Ogihara, M; Masaki, T; Watanabe, T; Hatano, K; Matsuda, K; Yahagi, N; Ichinose, M; Seichi, A; Muto, T
We describe herein the case of a psoas abscess complicating Crohn's disease, and present a review of the literature on this unusual disease entity. A 22-year-old Japanese man with a 5-year history of Crohn's ileocolitis presented with right lower abdominal and hip pain, and a diagnosis of right psoas abscess was subsequently made by abdominal computed tomography (CT). Following the administration of antibiotics and CT-guided percutaneous drainage of the abscess, the patient's symptoms temporarily improved; however, 2 weeks later, the abscess cavity was found to have extended around the periarticular tissue of the right hip joint. To prevent the development of septic arthritis of the hip joint, surgical drainage of the abscess cavity and ileocecal resection were immediately performed, after which the patient's condition greatly improved. The resected specimen showed Crohn's ileocolitis with an external fistula in the terminal ileum which was considered to have caused the psoas abscess. Since psoas abscess in Crohn's disease can result in serious complications such as septic arthritis of the hip joint if left untreated, aggressive treatment should be initiated without delay.
López Barbarín, J M; Lafuente Martínez, P; García Campos, F; Ibarra Peña, B; Díaz de Otazu, R
We report the case of a male patient with Crohn's disease associated with IgA nephropathy. He was treated surgically for the intestinal disorder and then with corticoids and sulfasalazine. Six years after treatment the patient was asymptomatic. As the intestinal situation improved there was concomitant normalization of urinary sediment, maintaining renal function. The fact that the digestive mucosa is one of the body's major sources of secretory IgA may account for the existence of a common for Crohn's disease and certain forms of IgA nephropathy.
Yang, Qingfan; Gao, Xiang; Chen, Huiping; Li, Miao; Wu, Xiaojian; Zhi, Min; Lan, Ping; Hu, Pinjin
To investigate the efficacy of exclusive enteral nutrition (EEN) in induction of remission in adult active Crohn's disease (CD) complicated with intestinal fistula/abdominal abscess or inflammatory intestinal stricture. Patients diagnosed with active CD with complications were recruited between July 2013 and July 2015. Patients were offered EEN for 12 weeks. Patients with abscess received antibiotic treatment with or without percutaneous drainage. Clinical variables were recorded (ClinicalTrials.gov Identifier: NCT02887287). Forty-one patients with CD and with intestinal fistula/abdominal abscess or inflammatory intestinal stricture aged 18-60 years, were included. Ten patients were accompanied with stenosis and 33 with intestinal fistula/abscess. After 12 weeks of EEN, the Crohn's disease activity index significantly decreased (223.43 ± 65.5 vs. 106.77 ± 42.73, p ≤ .001), and 80.5% of patients achieved full clinical remission totally. Fistula closure after EEN was observed in 75% of patients with entero-cutaneous fistula. In patients with stenosis, 20% had no response to EEN and were transferred for surgery. Partial remission and full remission were observed in 20% and 60% of patients after 12 weeks of EEN, respectively. Intra-abdominal abscess resolved in 76% of patients. Seventeen patients who had mucosal ulcers underwent colonoscopy before and after EEN, 47% achieved mucosal healing after the treatment. The inflammatory index of patients significantly decreased (p ≤ .01), nutritional parameters increased (p ≤ .01) and the European Nutritional Risk Screening (2002) decreased (p ≤ .01). EEN is effective in inducing early clinical remission, mucosal healing, promoting fistula closure and reducing the size of abscess in adult CD patients with complications.
Crohn's disease causes inflammation of the digestive system. It is one of a group of diseases called inflammatory ... small intestine called the ileum. The cause of Crohn's disease is unknown. It may be due to an ...
Levin, T L; Morton, E
Huge dose ACTH therapy is used in some severely ill patients with inflammatory bowel disease. We report a teenage girl with Crohn's disease who developed an acute abdomen following ACTH therapy. CT revealed the mass to be a hemorrhagic adrenal gland; the opposite adrenal gland was hypertrophied but without signs of hemorrhage.
Kerber, G W; Greenberg, M; Rubin, J M
Complications of Crohn's disease were demonstrated by computed tomography of the abdomen and pelvis in 7 patients. Four patients had developed abscesses, 2 located in the psoas region and 2 involving the retroperitoneum or the liver. Other abnormalities documented on CT included inflammatory masses, fistulae, carcinoma, mesenteric thickening, and extraintestinal complications such as gallstones, renal calculi, and sacroileitis. Computed tomography was found to be useful in the detection and follow-up of abdominal complications of Crohn's disease.
Smith, Chez; Kavar, Bhadrakant
A spinal epidural abscess is a neurosurgical emergency. Successful treatment frequently requires decompression of the spinal canal in combination with intravenous antibiotics. We report a patient with Crohn's disease who developed an extensive spinal epidural abscess communicating with an intra-abdominal collection.
Gore, R M; Cohen, M I; Vogelzang, R L; Neiman, H L; Tsang, T K
Abdominal and pelvic computed tomography (CT) scans were performed on 17 patients with suspected complications of Crohn's disease. CT was superior to conventional barium studies and colonoscopy in demonstrating mural, serosal, and mesenteric pathology such as bowel wall thickening (100%), abscess (59%) and phlegmon (6%) formation, and fibro-fatty proliferation of the mesentery (41%). While not advocated as the primary means of evaluating Crohn's disease, CT can provide information vital to the management of complications of this disease.
Salama, Muna; Lawrance, Ian-Craig
The anti-tumor necrosis factor (TNF)alpha medications demonstrate efficacy in the induction of remission and its maintenance in numerous chronic inflammatory conditions. With the increasing number of patients receiving anti-TNFalpha agents, however, less common adverse reactions will occur. Cutaneous eruptions complicating treatment with an anti-TNFalpha agent are not uncommon, occurring in around 20% of patients. Adalimumab, a fully humanized antibody against TNFalpha, may be expected to cause minimal immune-mediated skin reactions compared to the chimeric monoclonal antibody, infliximab. We, however, report a case of Stevens-Johnson syndrome that required hospitalization and cessation of adalimumab in a patient with Crohn's disease (CD). In this case report, a 29-year-old male with colonic and perianal CD with associated erythema nodosum and large joint arthropathy developed severe mucositis, peripheral rash and desquamation, fevers and respiratory symptoms concomitant with a second dose of 40 mg adalimumab after a 2 mo break from adalimumab therapy. Skin biopsies of the abdominal wall confirmed erythema multiforme and the patient was on no other drugs and infective etiologies were excluded. The patient responded rapidly to IV hydrocortisone and was able to be commenced on infliximab without recurrence of the Stevens-Johnson syndrome. Desquamating skin reactions have now been described in three of the TNFalpha antagonists (infliximab, etanercept and adalimumab). These reactions can be serious and prescribers need to be aware of the potential mucocutaneous side effects of these agents, especially as Stevens-Johnson syndrome is associated with significant morbidity and mortality.
Stappenbeck, Thaddeus S.; Rioux, John D.; Mizoguchi, Atsushi; Saitoh, Tatsuya; Huett, Alan; Darfeuille-Michaud, Arlette; Wileman, Tom; Mizushima, Noboru; Carding, Simon; Akira, Shizuo; Parkes, Miles; Xavier, Ramnik J.
Crohn disease (CD) is a chronic and debilitating inflammatory condition of the gastrointestinal tract.1 Prevalence in western populations is 100–150/100,000 and somewhat higher in Ashkenazi Jews. Peak incidence is in early adult life, although any age can be affected and a majority of affected individuals progress to relapsing and chronic disease. Medical treatments rely significantly on empirical corticosteroid therapy and immunosuppression, and intestinal resectional surgery is frequently required. Thus, 80% of patients with CD come to surgery for refractory disease or complications. It is hoped that an improved understanding of pathogenic mechanisms, for example by studying the genetic basis of CD and other forms of inflammatory bowel diseases (IBD), will lead to improved therapies and possibly preventative strategies in individuals identified as being at risk. PMID:20729636
... prognosis of Crohn's disease in adults. http://www.uptodate.com/home. Accessed June 2, 2014. Smoking and ... cancer surveillance in inflammatory bowel disease. http://www.uptodate.com/home. Accessed June 9, 2014. Inflammatory bowel ...
... large bowel ( colon ). Crohn's disease may lead to deep ulcers in the intestinal tract, giving a "cobblestone" ... understanding of the possible charges you will incur. Web page review process: This Web page is reviewed ...
Introduction Crohn's disease is a chronic condition of the gastrointestinal tract. It is characterised by transmural, granulomatous inflammation that occurs in a discontinuous pattern, with a tendency to form fistulae. The cause is unknown but may depend on interactions between genetic predisposition, environmental triggers, and mucosal immunity. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of medical treatments to induce remission in adults with Crohn's disease? What are the effects of surgical interventions to induce and maintain remission in adults with small-bowel Crohn's disease? What are the effects of surgical interventions to induce remission in adults with colonic Crohn's disease? What are the effects of medical interventions to maintain remission in adults with Crohn's disease; and to maintain remission following surgery? What are the effects of lifestyle interventions to maintain remission in adults with Crohn's disease? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 93 systematic reviews, RCTs, or observational studies that met our inclusion criteria. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: aminosalicylates, antibiotics, azathioprine/mercaptopurine, ciclosporin, corticosteroids (oral), enteral nutrition, fish oil, infliximab, methotrexate, probiotics, resection, segmental colectomy, smoking cessation, and strictureplasty. PMID:21524318
de Barros, Kátia Simone Cezário; Flores, Cristina; Harlacher, Luciana; Francesconi, Carlos Fernando Magalhães
The phenotypic expression of Crohn's disease may vary over time. Establishment of Crohn's disease phenotypes is important for definition of patient care strategies. The aim of the study was to evaluate the long-term evolution of patients based on disease phenotypes and the main factors associated with this evolution. Data from 179 patients were collected from a unicentric prospective database. Montreal classification was employed. Kaplan-Meier method was used to estimate the cumulative probability of complication development and surgery. Poisson regression for multivariate analysis was applied. The Local Institutional Review Board approved the research. Female: 54.2%. Mean age at diagnosis: 32.7 (±13.7) years. Behavior at presentation: inflammatory 62.0%, stricturing 24.6%, penetrating 13.4%; perianal disease: 31.8%; median follow-up time: 65.2 months (IQR 31.0-108.8). Behavior at follow-up period end: inflammatory 43.6%, stricturing 38.0%, penetrating 18.4%; perianal disease: 46.4%. Cumulative probability of being complication free in 5, 10, and 20 years: 86.3, 66.4, and 52.2%, respectively. Cumulative probability of being surgery free in 5, 10, and 20 years: 87.3, 79.2, and 64.1%, respectively. L1 and L4 locations, use of immunosuppressive therapy, smoking, number of hospitalization/patient-year, abdominal surgery, age at diagnosis <40 years, and biological therapy were the factors associated with changes in phenotype or development of complications and perianal disease. Clinical behavior altered in about one-third of patients. The most frequent complication was a change to stricturing pattern. Disease location, current smoker, immunosuppressive therapy use, hospitalization, and abdominal surgery were factors associated with an unfavorable clinical evolution.
Wu, Xiao-Li; Tao, Li-Ping; Wu, Jian-Sheng; Chen, Xiang-Rong
Aim. This study was performed to evaluate the additional enteral nutrition (EN) in the efficacy of infliximab (IFX) compared with the conventional therapy in managing Crohn's disease (CD) complicated with intestinal fistulas. Methods. A total of 42 CD with intestinal fistulas were randomly divided into infliximab treatment group (n = 20) and conventional therapy group (n = 22). We evaluated the laboratory indexes, Crohn's disease activity index (CDAI), Crohn's disease simplified endoscopic score (SES-CD), and healing of fistula in the two groups before treatment, at 14 weeks, and at 30 weeks, respectively. Results. In the IFX treatment group, the CDAI score, the SES-CD, erythrocyte sedimentation rate, and C-reactive protein levels were significantly decreased during treatment compared with those before treatment. The body mass index and albumin levels were increased in both groups. Moreover, in the IFX treatment group, fistula healing was found in 8 at the 14th week and 18 at the 30th week, respectively, which was greater than that in the conventional therapy group. Conclusion. Our study suggested that infliximab combined with EN is an effective treatment for CD patients complicated with intestinal fistulas. PMID:27738427
Posthuma, E F; Westendorp, R G; van der Sluys Veer, A; Kluin-Nelemans, J C; Kluin, P M; Lamers, C B
A 19 year old man with a history of Crohn's disease treated with azathioprine and prednisone, died after a primary infection with Epstein-Barr virus. He had the characteristics of the virus associated haemophagocytic syndrome, a rare complication of viral infections, which consists of fever, constitutional symptoms, hepatosplenomegaly, liver function and coagulation abnormalities, and hypertriglyceridaemia. Additionally, there was pain, cytopenia, and histiocytic hyperplasia in the bone marrow, spleen, or lymph nodes. This severe complication has been reported previously in renal transplant patients, but not in those with inflammatory bowel disease taking azathioprine. The immunosuppressive therapy may have contributed to this fatal complication of infectious mononucleosis, and this complication should be considered when treating a patient with inflammatory bowel disease with azathioprine. Images p312-a PMID:7883236
Diehl, S J; Lehmann, K J; Manthe, S; Georgi, M
Portal vein thrombosis is a rare complication of inflammatory bowel disease and occurs particularly in patients with ulcerative colitis. This report describes a patient with known Crohn's disease since 1980 who developed retroperitoneal abscesses and subsequently a septic portal vein thrombosis. After 10 years of remission, clinical deterioration, jaundice, and fever occurred. An abdominal CT-study confirmed the ultrasonic presumptive diagnosis of two retroperitoneal abscesses close to the pancreas tail. Another CT, one week later, showed furthermore a portal vein thrombosis. Only by intensive care treatment was it possible to control the critical situation.
Kala, Zdeněk; Marek, Filip; Válek, Vlastimil A; Bartušek, Daniel
Surgery of Crohns disease is an important part of the general treatment algorithm. The role of surgery is changing with the development of conservative procedures. The recent years have seen the return to early treatment of patients with Crohns disease. Given the character of the disease and its intestinal symptoms, a specific approach to these patients is necessary, especially regarding the correct choice of surgery. The paper focuses on the luminal damage of the small and large intestine including complications of the disease. We describe the individual indications for a surgical solution, including the choice of anastomosis or multiple / repeated surgeries.
Denis, Marie A; Cosyns, Jean-Pierre; Persu, Alexandre; Dewit, Olivier; de Galocsy, Chantal; Hoang, Pierre; Maldague, Philippe; Wallemacq, Pierre; Zerbib, Frank; Fiasse, René
Immunosuppressive drugs may prevent or partially reverse progression of renal AA-amyloidosis, a rare complication of Crohn's disease, often fatal due to renal failure. The clinical, biological and pathological data of 16 patients treated since 1976 were reviewed. Serum amyloid A was determined in surviving patients. The median age of the 16 patients (13 men) was 23·5 years (range 16-69). At Crohn's disease onset, Montreal phenotypes were similar to reported data. Out of 15 patients with renal insufficiency, 8 developed a nephrotic syndrome and 7 a low grade proteinuria. The single patient without renal insufficiency had nephrotic syndrome. A significant correlation (P < 0·05) between the extension of renal amyloid A and sclerosis was found in 12 patients. One patient had a 10 year remission of nephrotic syndrome with immunosuppressive drugs. In 6 patients treated with anti-TNF-α (Tumor-Necrosis-Factor-α) agents, anaphylactic reaction (1/6), death from septic shock (1/6), 5-year remission (1/6) or reduction of nephrotic syndrome (1/6) and stabilization of renal insufficiency (2/6) were observed. Surgery was performed in 10 patients. Kidney transplantation was performed in 5 of the 8 patients dialysed for end-stage renal failure. Among 6/16 patients (37%) still alive, 3 belong to the 5 transplanted patients (survival: 3-20 years) and 3 to the anti-TNF-α drugs treated patients; all but one exhibited a low serum amyloid A level. Suppression of Crohn's disease inflammation potentially leads to the control of amyloid A production, assessed by a decrease of serum amyloid A. Kidney transplantation provides a long survival. © 2013 The Authors. European Journal of Clinical Investigation © 2013 Stichting European Society for Clinical Investigation Journal Foundation.
Tonolini, Massimo; Ravelli, Anna; Campari, Alessandro; Bianco, Roberto
Pelvic osteomyelitis is a very uncommon complication of Crohn's disease, usually clinically unsuspected in the setting of acute Crohn's disease relapses. The case of a 21-year old patient is reported, in whom ileo-cecal inflammatory disease was complicated by fistulization to the presacral space and sacral osteomyelitis, plus multiple abscesses involving the iliopsoas, posterior paravertebral and gluteal muscles. As confirmed by surgical and pathological findings, MRI provided comprehensive imaging diagnosis by demonstrating both the pathogenesis and the full extent of the complex, deep pelvic inflammatory process. Low back pain in patients with Crohn's disease should not be underestimated since its differential diagnosis includes serious and potentially life-threatening causes such as osteomyelitis, so prompt assessment with cross sectional imaging, particularly MRI, is necessary.
... 2013;309(20):2150-2158. PMID: 23695484 www.ncbi.nlm.nih.gov/pubmed/23695484 . Fry RD, Mahmoud ... 2009;104(2):465-483. PMID: 19174807 www.ncbi.nlm.nih.gov/pubmed/19174807 . Sandborn WJ. Crohn's ...
Waljee, Akbar K.; Day, Nicholas M.; Bergmans, Carrie L.; Zahn, Katelin M.; Higgins, Peter D. R.; Wang, Stewart C.; Su, Grace L.
Background: Decisions between medical and surgical management of Crohn's disease (CD) incorporate risk assessments for potential complications of each therapy. Analytic morphomics is a novel method of image analysis providing quantifiable measurements of body tissue composition, characterizing body fat more comprehensively than body mass index alone. The aim of this study was to determine the risk factors associated with postoperative complications in CD, incorporating fat composition analysis using analytic morphomics. Methods: We performed a retrospective review of adults undergoing bowel resection for CD between 2004 and 2011 at a single center. Computed tomography obtained within 30 days prior to surgery underwent morphomic analysis for fat characterization. Postoperative infectious complications were defined as the need for a postoperative abdominal drain, intravenous antibiotics, or reoperation within 30 days. Bivariate and multivariate analyses using logistic regression were used to generate a prediction model of infectious complications. Results: A total of 269 subjects met selection criteria; 27% incurred postoperative infectious complications. Bivariate analysis showed hemoglobin, albumin, surgical urgency, high-dose prednisone use, and subcutaneous-to-visceral fat volume distribution as predictors of complications. Body mass index, anti-tumor necrosis factor alpha therapies, and immunomodulator use were not predictors of complication. Multivariate modeling demonstrated a c-statistic of 0.77 and a negative predictive value of 81.1% with surgical urgency (odds ratio = 2.78; 95% confidence interval, 1.46–6.02; P = 0.004), subcutaneous-to-visceral fat distribution (odds ratio = 2.01; 95% confidence interval, 1.20–3.19; P = 0.006), and hemoglobin (odds ratio = 0.69; 95% confidence interval, 0.55–0.85; P = 0.001) as predictors of infectious complication. Conclusions: Fat subtype and distribution are predictive of postoperative infectious complications
Pringle, Patricia L; Stewart, Kathleen O; Peloquin, Joanna M; Sturgeon, Holly C; Nguyen, Deanna; Sauk, Jenny; Garber, John J; Yajnik, Vijay; Ananthakrishnan, Ashwin N; Chan, Andrew T; Xavier, Ramnik J; Khalili, Hamed
Obesity is associated with systemic and intestine-specific inflammation and alterations in gut microbiota, which in turn impact mucosal immunity. Nonetheless, a specific role of obesity and its interaction with genetics in the progression of Crohn's disease (CD) is unclear. We conducted a cross-sectional study of patients with CD enrolled in Prospective Registry in Inflammatory Bowel Disease Study at Massachusetts General Hospital (PRISM). Information on diagnosis of CD and its complications were collected and confirmed through review of medical records. A genetic risk score was calculated using previously reported single-nucleotide polymorphisms-associated genome-wide with CD susceptibility. We used logistic regression to estimate the effect of body mass index (BMI) and its interaction with genetic risk on risk of CD complications. Among 846 patients with CD, 350 required surgery, 242 with penetrating disease, 182 with stricturing disease, and 226 with perianal disease. There were no associations between obesity (BMI ≥ 30 kg/m2) and risk of perianal disease, stricturing disease, or surgery. Compared with normal-weight individuals with BMI < 25 kg/m2, obesity was associated with lower risk of penetrating disease (odds ratio [OR = 0.56; 95% confidence interval [CI], 0.31-0.99). This association persists among a subgroup of participants with available BMI before development of penetrating disease (OR = 0.40; 95% CI, 0.16-0.88). There were no interactions between BMI and genetic risk score on risk of CD complications (all P interaction > 0.28). Our data suggest that obesity does not negatively impact long-term progression of CD, even after accounting for genetic predisposition.
Lu, Kim C; Hunt, Steven R
Although medical management can control symptoms in a recurring incurable disease, such as Crohn's disease, surgical management is reserved for disease complications or those problems refractory to medical management. In this article, we cover general principles for the surgical management of Crohn's disease, ranging from skin tags, abscesses, fistulae, and stenoses to small bowel and extraintestinal disease. Copyright © 2013 Elsevier Inc. All rights reserved.
Ihara, Yutaro; Hizawa, Kazuoki; Fujita, Kouhei; Iida, Masahiro; Washio, Ema; Kai, Takahiro; Nitahata, Tomoki; Esaki, Motohiro; Iida, Mitsuo
A 19-year-old woman, who had been receiving hormone replacement therapy for 13 months before the diagnosis of mosaic Turner syndrome (46XXp-/45X), developed Crohn's colitis and erythema nodosum of the lower legs. Colonoscopy revealed an anal fistula and the presence of deep longitudinal ulcers with cobblestoning in the colorectum. Therapy with prednisolone and adalimumab was effective for the intestinal and skin lesions. To date, all seven case reports of Turner syndrome in Japan have also developed Crohn's disease after hormone therapy, suggesting a possible association of sex hormones in the pathogenesis.
Guo, Kun; Ren, Jianan; Li, Guanwei; Hu, Qiongyuan; Wu, Xiuwen; Wang, Zhiwei; Wang, Gefei; Gu, Guosheng; Ren, Huajian; Hong, Zhiwu; Li, Jieshou
Surgical site infection (SSI) is the most common complication following surgical procedures. This study aimed to determine risk factors associated with SSI in patients with Crohn's disease (CD) complicated with gastrointestinal fistula. This was a retrospective review of patients who underwent surgical resection in gastrointestinal fistula patients with CD between January 2013 and January 2015, identified from a prospectively maintained gastrointestinal fistula database. Demographic information, preoperative medication, intraoperative findings, and postoperative outcome data were collected. Univariate and multivariate analysis was carried out to assess possible risk factors for SSI. A total of 118 patients were identified, of whom 75.4% were men, the average age of the patients was 34.1 years, and the average body mass index (BMI) was 18.8 kg/m(2). The rate of SSI was 31.4%. On multivariate analysis, preoperative anemia (P = 0.001, OR 7.698, 95% CI 2.273-26.075), preoperative bacteria present in fistula tract (P = 0.029, OR 3.399, 95% CI 1.131-10.220), and preoperative enteral nutrition (EN) <3 months (P < 0.001, OR 11.531, 95% CI 3.086-43.079) were predictors of SSI. Notably, preoperative percutaneous abscess drainage was shown to exert protection against SSI in fistulizing CD (P = 0.037, OR 0.258, 95% CI 0.073-0.920). Preoperative anemia, bacteria present in fistula tract, and preoperative EN <3 months significantly increased the risk of postoperative SSI in gastrointestinal fistula complicated with CD. Preoperative identification of these risk factors may assist in risk assessment and then to optimize preoperative preparation and perioperative care.
Bor, Renáta; Farkas, Klaudia; Bálint, Anita; Szűcs, Mónika; Ábrahám, Szabolcs; Milassin, Ágnes; Rutka, Mariann; Nagy, Ferenc; Milassin, Péter; Szepes, Zoltán; Molnár, Tamás
Magnetic resonance imaging (MRI) and transrectal sonography are the two accepted imaging modalities for evaluation of perianal fistulas and abscesses. Transperineal sonography is a new technique that is easy to learn and can be performed at any time. The purpose of this study was to prospectively compare the diagnostic accuracy of MRI, transrectal sonography, and transperineal sonography with surgical findings in patients with perianal Crohn disease. All patients with perianal Crohn disease underwent MRI, transrectal sonography, and transperineal sonography within a few days before surgery. Fistulas were classified as simple (43.8%) or complex (52.2%) based on surgical findings. Twenty-three patients with active perianal Crohn disease (12 women and 11 men; mean age, 29.9 years; current therapy: antibiotics, 69.6%; azathioprine, 56.5%; and biologics, 73.9%; previous surgery, 26.1%; and proportion of smokers, 39.1%) were included. Sensitivity values for MRI, transrectal sonography, and transperineal sonography for diagnosis of fistulas were 84.6%, 84.6%, and 100%, respectively. Transperineal sonography was more sensitive for diagnosis of perianal abscesses than MRI and transrectal sonography (100%, 58.8%, and 92.8%). Transperineal sonography is a very accurate diagnostic method with outstanding sensitivity compared with MRI and transrectal sonography for evaluation of complicated perianal Crohn disease. Due to its simplicity and low cost, it is recommended that transperineal sonography be the first diagnostic modality in these cases. © 2016 by the American Institute of Ultrasound in Medicine.
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Bosscha, K; van Vroonhoven, Th J M V
Two young women, aged 19 and 25 years, suffered from persistent perianal sepsis after local drainage of unusual gluteal abscesses. Preoperative CT scanning showed unrecognised and inadequately treated abscesses and signs of inflammatory bowel disease. Both patients underwent a reoperation: affected bowel segments were removed, stomas were created and abscesses were drained. In the case of unusual perianal abscesses the diagnosis 'Crohn's disease' must be considered. Preoperative examinations should include CT or MRI scans of the abdomen and pelvis. Intraoperative colonoscopy can often be helpful in assessing the extent of the affected bowel segment.
Asma, Sioud Dhrif; Soumaya, Youssef; Kahena, Jaber; Raouf, Dhaoui Mohamed; Nejib, Doss
Crohn disease is a chronic inflammatory disease characterized by sharply demarcated segments of gastrointestinal involvement from mouth to anus. Its perineal manifestations are among the most devastating and mutilating complications. They occur at any time and may precede the intestinal manifestations. Their most common presentations are perineal ulceration, fistula, and abscess. Proliferative and polypoid morphology of the cutaneous lesions mimicking warts and condyloma are rarely described. We report a 25-year-old woman with a 4-month history of confluent plaques of the perineal region with vegetant surfaces, suspected to be genital warts. The lesions progressed to fistulas, inducing deep ulcerations surrounded by pseudocondylomatous tumors. About 2 months prior to presentation she began to suffer from gastrointestinal symptoms and noted weight loss. Physical examination, endoscopic examination, and pathological interpretation led to the diagnosis of Crohn disease with perineal involvement being the initial presenting sign. Significant improvement was induced with prednisone (45 mg daily) and azathioprine. Our observation is notable for the pseudocondylomatous appearance and the dramatic response to medical treatment despite severe involvement.
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Hammami, Aya; Slama, Aida Ben; Jaziri, Hanen; Ameur, Wafa Ben; Mansour, Imed Ben; Brahem, Ahlem; Ajmi, Salem; Jemni, Hela; Ksiaa, Mehdi; Jmaa, Ali
Crohn's disease (CD) is characterized by transmural inflammation of the gastrointestinal tract, which predisposes to the formation of fistula. Duodenal involvement occurs in less than 5% of cases and often leads to clinically relevant strictures. However, fistula formation in the duodenum is exceptional. Herein, we report an unusual case of duodenobiliary fistula due to CD occurring in a 65-year-old patient who was successfully treated by anti-tumor necrosis factor (TNF) agents. This case report highlights the efficacy of anti-TNF alpha agents in the treatment of a bilioenteric fistula because it increases the probability of clinical remission and mucosal healing and therefore reduces the need for surgical treatment which may be associated morbidity.
Chon, Hyung Ku; Shin, Ik Sang; Kim, Sang Wook
Endoscopic treatments have emerged as an alternative to surgery, in the treatment of benign colorectal stricture. Unlike endoscopic balloon dilatation, there is limited data on endoscopic electrocautery incision therapy for benign colorectal stricture, especially with regards to safety and long-term patency. We present a case of a 29-year-old female with Crohn's disease who had difficulty in defecation and passing thin stools. A pelvic magnetic resonance imaging scan, gastrograffin enema, and sigmoidoscopy showed a high-grade anorectal stricture. An endoscopic insulated-tip knife incision was successfully performed to resolve the problem. From our experience, we suggest that endoscopic insulated-tip knife treatment may be a feasible and effective modality for patients with short-segment, very rigid, fibrotic anorectal stricture. PMID:27433152
Biller, J A; Grand, R J; Harris, B H
Little information is available about the development of abdominal abscesses in adolescents with Crohn's disease. We report the clinical presentation of five adolescents with Crohn's disease who developed this complication. The mean time from diagnosis until development of an abdominal abscess was 1.7 years. The admitting diagnosis was an acute abdomen in two patients and recurrent Crohn's disease in the other three. No features of the clinical presentation or laboratory data distinguished this group from other adolescents with Crohn's disease. The use of ultrasound and CT scanning was helpful in making this diagnosis preoperatively. Those patients with active Crohn's disease who do not respond promptly to medical therapy should be evaluated for the development of this complication.
Kammann, Steven; Menias, Christine; Hara, Amy; Moshiri, Mariam; Siegel, Cary; Safar, Bashar; Brandes, Steven; Shaaban, Akram; Sandrasegaran, Kumar
A relatively large proportion of patients with Crohn disease (CD) develop complications including abscess formation, stricture, and penetrating disease. A subset of patients will have genital and reproductive organ involvement of CD, resulting in significant morbidity. These special circumstances create unique management challenges that must be tailored to the activity, location, and extent of disease. Familiarity with the epidemiology, pathogenesis, imaging features, and treatment strategies for patients with genital CD can aid imaging diagnoses and guide appropriate patient management. The purpose of this study is to illustrate the spectrum of CD in the genital tract and reproductive organs and discuss the complex management strategies in these patients as it relates to imaging. Given the impact on patient outcome and treatment planning, familiarity with the epidemiology, pathogenesis, imaging features, and treatment of patients with genital Crohn disease can aid radiologic diagnoses and guide appropriate patient management.
Akazawa, Yuko; Takeshima, Fuminao; Yajima, Hiroyuki; Imanishi, Daisuke; Kanda, Tsutomu; Matsushima, Kayoko; Minami, Hitomi; Yamaguchi, Naoyuki; Ohnita, Ken; Isomoto, Hajime; Hayashi, Tomayoshi; Nakashima, Masahiro; Nakao, Kazuhiko
Common variable immune deficiency is the most frequently encountered immunodeficiency in adults, which is characterized by low levels of serum immunoglobulins. Common variable immune deficiency can present with inflammatory bowel disease-like colitis because of the dysregulated immune system; paradoxically activated T cell receptor pathways are thought to be pivotal in pathogenesis of common variable immune deficiency-related colitis. Treatment for severe complications, such as gastrointestinal bleeding, is not established. We report a case of common variable immune deficiency-related Crohn's-like disease presenting massive melena, which was successfully treated by short course infliximab therapy. A 26-year-old Japanese man with history of common variable immune deficiency presented with diarrhea, abdominal pain, and fever. Venous administration of antibiotics did not improve his symptoms. Colonoscopy revealed multiple longitudinal ulcers as well as cobblestone-like change in the ileum end and the ascending colon. Histopathological examination of biopsy specimen showed erosion and infiltration of T lymphocytes with lack of B cells. Intravenous hyperalimentation, mesalazine, and steroid did not improve the symptoms and the patient subsequently presented with massive melena. Colonoscopy revealed a protuberant vessel on one of the ulcers in the ascending colon. Endoscopic clipping was repeatedly performed for hemostasis, which was only temporarily successful. In an attempt to manage the bleeding and colitis, a trial of infliximab was given on week 0, week 2 and week 6. Gastrointestinal hemorrhage from the ulcer halted immediately after the first infliximab injection. Colonoscopy performed after the third infliximab showed remarkable improvement in the ileocolitis. No evidence of increased susceptibility to infections was observed and the patient has been in clinical remission for 3 years. We present this case together with review of literature to share our experience
Fernandez-Flores, Angel; Dajil, Saleh
We report a 20-year-old man who presented with abdominal discomfort for 2 months. Colonoscopy showed skip areas with ulceration, resembling Crohn's disease. Biopsies showed chronic inflammation and a non-necrotizing granuloma. An adult pinworm was found in the lumen from an uninvolved segment. The patient responded to mebendazole.
Garcia-Diaz, M.; Mira, M.; Nevado, L.; Galván, A.; Berenguer, A.; Bureo, J. C.
Although systemic vasculitis can be a complication of inflammatory bowel disease at several locations (skin, eyes, brain, mesentery, and lung) the association of retinal vasculitis with Crohn's disease is rare. We studied a 26-year-old woman with biopsy-demonstrated Crohn's disease who developed a severe bilateral retinal arteritis and phlebitis, with acute loss of vision. Images Figure 1 Figure 2 PMID:7746779
Gaspar, Sandro Roberto da Silva; Mendonça, Tiago; Oliveira, Pedro; Oliveira, Tiago; Dias, José; Lopes, Tomé
Objective: To present an updated description of the relation between Crohn's disease (CD) and Urolithiasis. Patients and Methods: A literature search for English-language original and review articles was conducted in Medline, Embase, and Cochrane databases in the month of December 2014 for papers either published or e-published up to that date, addressing the association between CD and urolithiasis as its consequence. All articles published in English language were selected for screening based on the following search terms: “CD,” “renal calculus,” “IBD,” and “urolithiasis.” We restricted the publication dates to the last 15 years (2000–2014). Results: In total, 901 patients were included in this review of which 95 were identified as having CD and urolithiasis simultaneously, for a total of 10.5%. Average age was 45.07 years old, irrespective of gender. 28.6% of patients received some kind of medical intervention without any kind of surgical technique involved, 50% of patients were submitted to a surgical treatment, and the remaining 21.4% were submitted to a combination of surgical and medical treatment. Urolithiasis and pyelonephritis incidence ranged from 4% to 23% with a risk 10–100 times greater than the risk for general population or for patients with UC, being frequent in patients with ileostomy and multiple bowel resections. We found that urolithiasis occurred in 95 patients from a total of 901 patients with CD (10.5%); 61.81% in men and 38.19% in women. Stone disease seems to present approximately 4–7 years after the diagnosis of bowel disease and CaOx seems to be the main culprit. Conclusions: CD is a chronic, granulomatous bowel disease, with urolithiasis as the most common extraintestinal manifestation (EIM), particularly frequent in patients submitted to bowel surgery. This complication needs to be recognized and addressed appropriately, especially in patients with unexplained renal dysfunction, abdominal pain, or recurrent urinary
Parray, Fazl Q; Wani, Mohd Lateef; Bijli, Akram H; Thakur, Natasha; Irshad, Ifat
Crohn's disease (CD) is known for wide anatomic distribution, different presentations, life-threatening complications, and multiple modalities of management. Its multiple implications are still unaddressed. Since all the patients do not show a good response to medical modalities of treatment, a significant percentage of these patients are referred to the surgeon for the palliation of complications or for the ultimate curative treatment. Since most surgeons come across such patients only rarely, it is sometimes difficult for them to choose the appropriate procedure at the time of need. Moreover, the various surgical modalities available for the different presentations and complications of the disease have not been adequately discussed. The aim of this review is to offer insight and a detailed account of the management of CD from a surgical perspective. This review offers an overview of the various surgical options available, their utility in context, and an approach to various scenarios of complicated CD.
Rodriguez, Pablo; Mendez, Ramiro; Matute, Fatima; Hernandez, Paula; Mendoza, Juan Luis
Magnetic resonance enterography in Crohn disease management has been rapidly growing in importance during recent years. Being familiar to this technique is essential for radiologists and also, to some extent, for gastroenterologists. Our aim is to study and describe the imaging findings in magnetic resonance enterography in Crohn disease to develop a comprehensive and useful review article and imaging atlas.
Cheifetz, Adam S
Treatment of Crohn disease is rapidly evolving, with the induction of novel biologic therapies and newer, often more intensive treatment approaches. Knowing how to treat individual patients in this quickly changing milieu can be a challenge. To review the diagnosis and management of moderate to severe Crohn disease, with a focus on newer treatments and goals of care. MEDLINE was searched from 2000 to 2011. Additional citations were procured from references of select research and review articles. Evidence was graded using the American Heart Association level-of-evidence guidelines. Although mesalamines are still often used to treat Crohn disease, the evidence for their efficacy is lacking. Corticosteroids can be effectively used to induce remission in moderate to severe Crohn disease, but they do not maintain remission. The mainstays of treatment are immunomodulators and biologics, particularly anti-tumor necrosis factor. Immunomodulators and biologics are now the preferred treatment options for Crohn disease.
Cheikh, Imed; Ben Ammar, Ahmed; Essid, Mejda; Azzouz, Messadak; Ettahri, Nabil; Krichene, Mohamed; Bouzaidi, Slim; Ennajar, Taoufik
The purpose of this study was to estimate and achieve the factors that have an influence on the evolution of the Chron's disease. This study was done in 124 patients reaching the diagnosis of Chron's disease between 1988 and 1997. The evolution of this disease was achieved in 87 patients. The Chron's disease was inactive among 31 patients (35-6%)--with discontinous evolution in 42 patients (48.3%) and active chronic in 14 patients (16-1%). The active chronic form of Chron's disease was twice more frequent among the smokers and the patients with age above 40 years--but this difference has no statistical significance. The indication of surgical treatment was realised in 21 patients and it takes place as result of failure of medical treatment in 16 patients (76-2%)--an abcess in 2 patents (9-5%) and iatrogenic perforation in 1 patient (4-8%). The age-sexe-smoke--the intensity of the initial attack and the nature of the treatment had no influence in the need of the surgical interfference. The Chron's disease showed the less severe evolution in this study--the age above 40 years and the consumption of smoke increased the frequency of active chronic form.
Bettenworth, Dominik; Nowacki, Tobias M; Friedrich, Alexander; Becker, Karsten; Wessling, Johannes; Heidemann, Jan
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 IBD-specific treatment.
Wilkins, Thad; Jarvis, Kathryn; Patel, Jigneshkumar
Crohn's disease is a chronic inflammatory condition affecting the gastrointestinal tract at any point from the mouth to the rectum. Patients may experience diarrhea, abdominal pain, fever, weight loss, abdominal masses, and anemia. Extraintestinal manifestations of Crohn's disease include osteoporosis, inflammatory arthropathies, scleritis, nephrolithiasis, cholelithiasis, and erythema nodosum. Acute phase reactants, such as C-reactive protein level and erythrocyte sedimentation rate, are often increased with inflammation and may correlate with disease activity. Levels of vitamin B12, folate, albumin, prealbumin, and vitamin D can help assess nutritional status. Colonoscopy with ileoscopy, capsule endoscopy, computed tomography enterography, and small bowel follow-through are often used to diagnose Crohn's disease. Ultrasonography, computed axial tomography, scintigraphy, and magnetic resonance imaging can assess for extraintestinal manifestations or complications (e.g., abscess, perforation). Mesalamine products are often used for the medical management of mild to moderate colonic Crohn's disease. Antibiotics (e.g., metronidazole, fluoroquinolones) are often used for treatment. Patients with moderate to severe Crohn's disease are treated with corticosteroids, azathioprine, 6-mercaptopurine, or anti-tumor necrosis factor agents (e.g., infliximab, adalimumab). Severe disease may require emergent hospitalization and a multidisciplinary approach with a family physician, gastroenterologist, and surgeon.
Chaudhry, Naueen A; Riverso, Michael; Grajo, Joseph R; Moser, Patricia P; Zou, Fei; Homsi, Maher; Punglia, Darashana R; Zimmermann, Ellen M
Patients with Crohn's disease (CD) typically undergo multiple cross-sectional imaging exams including computed tomography and magnetic resonance enterography during the course of their disease. The aim was to identify imaging findings that predict future disease-related poor outcomes. This was a retrospective, case control study at a single tertiary center. Cases were CD patients diagnosed with complications (bowel obstruction, perforation, internal fistula, or abscess); controls were CD patients without complications. Two radiologists blinded to clinical outcomes, independently scored cross-sectional imaging examinations obtained before the complication. One hundred eight patients (67 F; 41 M) with CD (51 cases; 57 controls) were included. For the cases, 21 had internal fistulae, 15 had bowel obstructions, 13 had abdominal abscesses, and 2 developed bowel perforations. Patients with complications were more likely to have a fixed small bowel stricture on cross-sectional imaging (P = 0.01). A patient with a stricture and upstream dilatation was 3.4 times more likely to develop a complication in the next 2 years. When present in the setting of hypervascularity and/or evidence of active inflammation, the risk increased further to 15-fold. Cases were more likely to be active smokers (29% versus 12%, P = 0.033). Cases had more evidence of inflammation based on higher Harvey Bradshaw Index values and inflammatory biomarkers and lower hemoglobin values. Information from radiologic studies, especially the presence of fixed strictures, can predict future CD complications. These findings, along with smoking and ongoing inflammation, should alert the clinician to the possibility of future complications.
Maheshwari, Gargi R.; Mehta, Hita H.; Jhamwar, Mugdha M.
Cutaneous Crohn's or anogenital granulomatosis is a rare disorder, which presents commonly as swelling and erosions on anogenital area and associated with features of intestinal Crohn's disease. We report a case of 23-year-old female who presented with vitiligo patches on back and legs for 1-year, painful edema and ulcers on anogenital area and oral cavity for 9 months and diarrhea with bleeding per annum for 1 month. Features on ultrasonography, multislice computed tomography scan, colonoscopy, and biopsy from nodule on anal wall were suggestive of granulomatous Crohn's disease. Thus, we present the case due to its rarity. PMID:24958989
Feuerstein, Joseph D; Cheifetz, Adam S
Crohn disease is a chronic idiopathic inflammatory bowel disease condition characterized by skip lesions and transmural inflammation that can affect the entire gastrointestinal tract from the mouth to the anus. For this review article, we performed a review of articles in PubMed through February 1, 2017, by using the following Medical Subject Heading terms: crohns disease, crohn's disease, crohn disease, inflammatory bowel disease, and inflammatory bowel diseases. Presenting symptoms are often variable and may include diarrhea, abdominal pain, weight loss, nausea, vomiting, and in certain cases fevers or chills. There are 3 main disease phenotypes: inflammatory, structuring, and penetrating. In addition to the underlying disease phenotype, up to a third of patients will develop perianal involvement of their disease. In addition, in some cases, extraintestinal manifestations may develop. The diagnosis is typically made with endoscopic and/or radiologic findings. Disease management is usually with pharmacologic therapy, which is determined on the basis of disease severity and underlying disease phenotype. Although the goal of management is to control the inflammation and induce a clinical remission with pharmacologic therapy, most patients will eventually require surgery for their disease. Unfortunately, surgery is not curative and patients still require ongoing therapy even after surgery for disease recurrence. Importantly, given the risks of complications from both Crohn disease and the medications used to treat the disease process, primary care physicians play an important role in optimizing the preventative care management to reduce the risk of complications. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
Li, Yi; Stocchi, Luca; Cherla, Deepa; Liu, Xiaobo; Remzi, Feza H
The use of narcotics among patients with Crohn disease (CD) is endemic. To evaluate the association between preoperative use of narcotics and postoperative outcomes in patients with CD. Patients undergoing abdominal surgery for CD at a tertiary referral center between January 1998 and June 2014 were identified from an institutional prospectively maintained CD database. Primary end points were overall morbidity, postoperative hospital length of stay, and readmission. Univariate and multivariate analyses were used to assess possible associations between postoperative outcomes and demographic and clinical variables, including preoperative narcotic use. Of the 1331 patients included, the mean age for patients who had at least 1 pharmacy claim for narcotics within 1 month before surgery was 41.5 years and 41.1 years for patients without a pharmacy claim. Of 1461 abdominal operations for CD, 267 (18.3%) were performed on patients receiving preoperative narcotics. Patients receiving narcotics were more likely to have a current smoking habit (P < .001) with perianal disease (P = .046) and undergoing treatment with biologics (P = .04). Patients with preoperative narcotic use had a longer mean (SD) length of stay (11.2 [8.9] vs 7.7 [5.5]; P < .001) and were more likely to develop postoperative complications (52.8% vs 40.8%; P < .001). Multivariable analysis indicated that preoperative narcotic use was the only independent risk factor associated with both postoperative morbidity (odds ratio = 1.36; 95% CI = 1.02-1.82; P = .04) and prolonged hospital stay (estimate = 2.91; SE = 0.44; P < .001). Subgroup analysis indicated that outpatient narcotic users had increased incidence of adverse postoperative outcomes compared with inpatient-only narcotic users. Preoperative use of narcotics in patients undergoing abdominal surgery for CD is associated with worse postoperative outcomes. Before starting regular narcotic use, patients with
Sheedy, Shannon P; Bruining, David H; Dozois, Eric J; Faubion, William A; Fletcher, Joel G
Pelvic magnetic resonance (MR) imaging is currently the standard for imaging perianal Crohn disease. Perianal fistulas are a leading cause of patient morbidity because closure often requires multimodality treatments over a prolonged period of time. This review summarizes clinically relevant anal sphincter anatomy, imaging methods, classification systems, and treatment objectives. In addition, the MR appearance of healing perianal fistulas and fistula complications is described. Difficult imaging tasks including the assessment of rectovaginal fistulas and ileoanal anastomoses are highlighted, along with illustrative cases. Emerging innovative treatments for perianal Crohn disease are now available and have the promise to better control sepsis and maintain fecal continence. Different treatment modalities are selected based on fistula anatomy, patient factors, and management goals (closure versus sepsis control). Radiologists can help maximize patient care by being familiar with MR imaging features of perianal Crohn disease and knowledgeable about what features may influence therapy decisions. (©) RSNA, 2017 Online supplemental material is available for this article.
Hegnhøj, J; Hansen, C P; Rannem, T; Søbirk, H; Andersen, L B; Andersen, J R
We investigated exocrine pancreatic function in a population of patients with Crohn's disease in order to correlate the pancreatic function with clinical and laboratory variables. A total of 143 patients affected by Crohn's disease and 115 control subjects were studied. All had a Lundh meal test. As a group patients with Crohn's disease had significantly decreased activity of both amylase (p less than 0.02) and lipase (p less than 0.001) in duodenal aspirates. In patients with Crohn's disease enzyme activities were not correlated to duration of disease or to extent or localisation of previous bowel resection. The lowest enzyme values were found in patients with the most extensive bowel involvement, and they were significantly lower (p less than 0.05) than in patients with disease confined to the terminal ileum. The differences between enzyme values in other subgroups of patients were not significant. For the patient group as a whole no correlation was found between disease activity and enzyme values, but for the most uniform group of patients, those with terminal ileitis, pancreatic function was significantly lower (p less than 0.05) in patients with moderate and severe disease compared with patients with mild disease. Thus at least two factors seem to be responsible for impaired pancreatic function in Crohn's disease: firstly disease activity and secondly localisation or extent of disease. PMID:1698692
Crohn disease (often seen in the literature as "Crohn's disease"), an autoimmune disease with debilitating gastrointestinal and extragastrointestinal manifestations, is on the rise in the United States and Europe. This article discusses the disease process, clinical presentation, diagnostic tools, and treatment options for Crohn disease. Statistics regarding disease prevalence and epidemiology also are reported.
Jasdanwala, Sarfaraz; Babyatsky, Mark
Crohn's disease, a transmural inflammatory bowel disease, has many well-known extra-intestinal manifestations and complications. Although acute pancreatitis has a higher incidence in patients with Crohn's disease as compared to the general population, acute pancreatitis is still relatively uncommon in patients with Crohn's disease. Patients with Crohn's disease are at an approximately fourfold higher risk than the general population to develop acute pancreatitis. The risk of developing acute pancreatitis is higher in females as compared to males. Acute pancreatitis can occur at any age with higher incidence reported in patients in their 20s and between 40-50 years of age. The severity and prognosis of acute pancreatitis in patients with Crohn's disease is the same as in general population. Acute pancreatitis can occur before onset of intestinal Crohn's disease, this presentation being more common in children than adults. It can also occur as the presenting symptom. However, most commonly it occurs after intestinal symptoms have manifest with a mean time interval between the initial presentation and development of acute pancreatitis being 2 years. There are several etiological factors contributing to acute pancreatitis in patients with Crohn's disease. It is not clear whether acute pancreatitis is a direct extra-intestinal manifestation of Crohn's disease; however, majority of the cases of acute pancreatitis in patients with Crohn's disease are due to GS and medications. Drugs used for the treatment of Crohn's disease that have been reported to cause acute pancreatitis include 5-ASA agents, azathioprine and 6 mercaptopurine, metornidazole and corticosteroids. Recent evidence has emerged correlating both type 1 and 2 autoimmune pancreatitis with Crohn's disease. Understanding the association between the two disease entities is key to effectively manage patients with Crohn's disease and acute pancreatitis.
Hagen, Joshua W; Swoger, Jason M; Grandinetti, Lisa M
Awareness of the extraintestinal manifestations of Crohn disease is increasing in dermatology and gastroenterology, with enhanced identification of entities that range from granulomatous diseases recapitulating the underlying inflammatory bowel disease to reactive conditions and associated dermatoses. In this review, the underlying etiopathology of Crohn disease is discussed, and how this mirrors certain skin manifestations that present in a subset of patients is explored. The array of extraintestinal manifestations that do not share a similar pathology, but which are often seen in association with inflammatory bowel disease, is also discussed. Treatment and pathogenetic mechanisms, where available, are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.
Goischke, H K; Ochsendorf, F R
We report 2 patients with the association of Crohn's disease and acne inversa (= hidradenitis suppurativa). A 50-year-old woman with a 10-year-history of Crohn's disease developed suppurative nodules and abscesses in the genitoanal region. Over several years these lesions were hidden from everybody including the family physician. In a 42-year-old female patient abscesses appeared in the axilla 4 years after the diagnosis of Crohn's disease. During the next years these draining lesions also developed in both groins and the perineum. The differential diagnosis included cutaneous manifestations of Crohn's disease in both cases. The clinical picture with draining abscesses and sinuses with communicating channels, cystic nodules, hypertrophic scars and foul-smelling discharge were typical findings of acne inversa. In the last years this entity was reported several times in patients with Crohn's disease. Acne inversa starts with a compact hyperkeratosis of the infundibulum in terminal hair follicles, followed by a segmental rupture of the follicular epithelium and a spreading inflammatory reaction. As pathogenic factors genetic disposition and smoking were discussed. The only curative therapy is excision of the affected area. The reported association should be known in order to recognize the disease and institute the right therapy.
Dai, Shi-Xue; Gu, Hong-Xiang; Lin, Qian-Yi; Wu, Yan-Kun; Wang, Xiao-Yan; Huang, Shao-Zhuo; Xing, Tiao-Si; Chen, Min-Hua; Zhang, Qing-Fang; Zheng, Zhong-Wen; Sha, Wei-Hong
Crohn disease (CD) with complications such as penetrating, stricturing, and perianal disease is called complicated CD. The aim of this study is to test the efficiency with which the CD8CD28/CD8CD28 cell balance can predict a subsequent active stage in patients with newly diagnosed complicated CD.Seventeen patients with complicated CD and 48 CD patients with no complications were enrolled. Blood CD8 T cells were tested from all of the 65 newly diagnosed CD patients upon enrollment. The potential risk factors were compared between the 2 groups. A 30-week follow-up was performed, and the efficiency of the CD8 cell balance at predicting active CD was analyzed using receiver-operating characteristic curves. The cumulative remission lasting rates (CRLRs) were analyzed using the Kaplan-Meier method.Compared with the control CD group, patients with complicated CD were predominantly male and younger in age; they also had lower body mass indices (BMIs), higher Crohn disease activity indices (CDAIs), higher immunosuppressant and steroid prescription rates, and significantly higher surgical rates. The CD8CD28/CD8CD28 balance was associated with BMI, CDAI, steroids, and surgery. The CD8CD28/CD8CD28 ratios were significantly lower at week 0 and on the 6th, 22nd, and 30th week during follow-up with a shorter lasting time of remission for the complicated CD patients. The CD8CD28/CD8CD28 ratio could accurately predict the active stage for the patients with complicated CD, and the highest sensitivity (89.2%) and specificity (85.3%) were found when the ratio was 1.03. Treatment with steroids and surgery, along with a significantly lower CD8CD28/CD8CD28 ratio and lower CRLRs, was closely related to a worse outcome for the patients with complicated CD.Patients requiring steroids and surgery experience more severe disease activity and thus a disequilibrated immunological balance, which could be the main reason for a decreased CD8CD28/CD8CD28 ratio. This ratio can sensitively predict the
Moghadamyeghaneh, Zhobin; Carmichael, Joseph C; Mills, Steven D; Pigazzi, Alessio; Stamos, Michael J
There is limited data regarding outcomes of bowel resection in patients with Crohn's disease. We sought to investigate complications of such patients after bowel resection. The Nationwide Inpatient Sample databases were used to examine the clinical data of Crohn's patients who underwent bowel resection during 2002 to 2012. Multivariate regression analysis was performed to investigate outcomes of such patients. We sampled a total of 443,950 patients admitted with the diagnosis of Crohn's disease. Of these, 20.5 per cent had bowel resection. Among patients who had bowel resection, 51 per cent had small bowel Crohn's disease, 19.4 per cent had large bowel Crohn's disease, and 29.6 per cent had both large and small bowel Crohn's disease. Patients with large bowel disease had higher mortality risk compared with small bowel disease [1.8% vs 1%, adjusted odds ratio (AOR): 2.42, P < 0.01]. Risks of postoperative renal failure (AOR: 1.56, P < 0.01) and respiratory failure (AOR: 1.77, P < 0.01) were higher in colonic disease compared with small bowel disease but postoperative enteric fistula was significantly higher in patients with small bowel Crohn's disease (AOR: 1.90, P < 0.01). Of the patients admitted with the diagnosis of Crohn's disease, 20.5 per cent underwent bowel resection during 2002 to 2012. Although colonic disease has a higher mortality risk, small bowel disease has a higher risk of postoperative fistula.
Farraye, Francis A.
A Crohn's disease patient's first visit to a new practice is the optimal time to collect important clinical data and identify appropriate therapies. A methodologic approach to this visit is crucial. The focus of this visit should be on preparing the patient for the initiation of treatment, with particular attention to the necessary steps prior to the use of immunosuppressive and biologic agents. This paper is intended to provide recommendations and a checklist for the initial assessment and evaluation of patients with Crohn's disease. PMID:21528042
Patti, R; Arcara, M; Daví, V; Leo, P; Di Vita, G
Free perforation in abdominal cavity in patients with Crohn's disease is a rare entity as attested from the data reported in the literature. It is a very dangerous event and requires a surgical urgency management. The Authors reported two cases of free perforation, in patients with Crohn' disease, undergoing surgical operation in urgency. Analyzing pathogenesis, difficulty in diagnosis making and therapeutic choices, they underline that CT is very useful in the diagnosis, while resection of the perforated intestinal tract represent the best surgical treatment.
Sakala, Michelle D; Dillman, Jonathan R; Ladino-Torres, Maria F; McHugh, Jonathan B; Adler, Jeremy
Crohn disease, a form of chronic inflammatory bowel disease is characterized by discontinuous inflammatory lesions of the gastrointestinal tract, has a variety of behavioral patterns, including penetrating or fistulous disease. While magnetic resonance enterography (MRE) excellently depicts inflamed bowel segments, it can also be used to assess for a variety of Crohn-disease-related extraintestinal complications, including fistulae. We present the MRE findings of a complex ileocolovesicular fistula in a 14-year-old boy with Crohn disease, where the fistulous tract to the urinary bladder was best delineated on precontrast T1-W imaging because of the presence of fecal material.
Fong, Steven C M; Irving, Peter M
Small bowel Crohn's disease can present with clinical challenges that are specific to its location. In this review, we address some of the areas that present particular problems in small bowel Crohn's disease. A key issue specific to small bowel Crohn's disease relates to its diagnosis given that access to the small bowel is limited. Radiological advances, particularly in small bowel ultrasonography and MRI, as well as the introduction of capsule endoscopy and balloon enteroscopy are helping to address this. In addition, our ability to differentiate small bowel Crohn's disease from other causes of inflammation, such as tuberculosis, is improving on the basis of better understanding of the features that differentiate these conditions. It is also becoming apparent that jejunal Crohn's disease represents a distinct disease phenotype with potentially worse clinical outcomes. Finally, because it is a rare complication, our understanding of small bowel cancer associated with Crohn's disease remains limited. Recent publications are, however, starting to improve our knowledge of this condition. Although small bowel Crohn's disease presents specific management issues not seen in patients with Crohn's disease elsewhere in the gastrointestinal tract, our knowledge of how to manage these is improving.
... page: https://medlineplus.gov/news/fullstory_164622.html New Meds Make Inroads Against Crohn's Disease Study finds ... hospital than in the past, according to a new federal study. Crohn's is a chronic inflammatory bowel ...
Noyer, C M; Brandt, L J
Perineal lesions are a frequent and troublesome complication of Crohn's disease. Although there are various surgical and medical therapeutic regimens available to treat these lesions, all have significant associated morbidity, mortality, and toxicity. Recently, the beneficial effects of hyperbaric oxygen therapy (HBOT) have been described in patients with severe or refractory perineal disease, but the role of HBOT in larger groups or less severely affected patients has not yet been studied, nor has the minimum number of treatments required for initial or complete healing of perineal disease in this population been described. This article reviews the known and theoretical tissue effects of HBOT and discusses its potential role in treating patients with perineal Crohn's disease.
Gillen, C D; Andrews, H A; Prior, P; Allan, R N
The colorectal cancer risk in Crohn's disease eliminating all known biases was assessed in a cohort of 281 patients with Crohn's disease who resided in the West Midlands at the time of diagnosis, and were first seen within five years of onset of symptoms between 1945-1975. All patients were 15 years of age or more at onset and were followed up from 12-35 years (total 5213 person years at risk (PYR)). The colorectal cancer risk in the series compared with the risk in the general population was computed by applying sex and age specific PYRs to the date of death or end of the study period 31 December 1991. There were six colonic and two rectal cancers. Six of the eight colorectal cancers were diagnosed 20 or more years after the onset of Crohn's disease. The relative risk (RR) of colorectal cancer for the series as a whole was 3.4 (p < 0.001), with a fivefold excess in the colon, but no significant excess in the rectum. Patients with extensive colitis showed an 18-fold increase in risk (RR = 18.2, p < 0.001), which decreased with increasing age at onset. This study shows that there is a statistical excess risk of developing colorectal cancer in patients who develop their Crohn's disease at a young age of onset (less than 30 years of age). PMID:8200559
Andreani, S M; Dang, H H; Grondona, P; Khan, A Z; Edwards, D P
Crohn's disease is characterized by transmural bowel inflammation and a tendency to form fistulas with adjacent structures. Several different fistulas have been described: enterocutaneous, enteroenteric, enterovesical, enterovaginal, and perineal. Rectovaginal fistulas are difficult to treat despite multimodal therapy. This study was designed to review the current strategic options to best manage this condition. We reviewed the English-language literature from 1966 to 2006, using PUBMED, targeting Crohn's disease involving vagina using key words "rectovaginal fistula and CD," "anovaginal fistula and CD," "anovaginal fistula," and "rectovaginal fistula." We excluded the involvement of the vagina from a pouch after a proctectomy. A total of 776 articles were found; 206 articles were identified and judged as being relevant on the basis of title-related articles and links were reviewed. Fifty-three articles were selected after reading the abstract or full manuscript. The management of rectovaginal fistula, representing 9 percent of all fistulas, remains a challenge in the setting of Crohn's disease. Medical treatments are not favorable with low rates of long-term symptomatic control and unacceptable high rates of recurrence. Several novel and new surgical techniques have been described, and rectal advancement flap, in selected patients, seems to have the most successful results. The management of rectovaginal fistula of Crohn's origin should involve both gastroenterologists and coloproctologists, with the best surgical results being achieved in patients receiving optimum medical therapy. More focused studies targeting these patients with the use of combined medical and surgical therapy are necessary.
Al-Hawary, Mahmoud M; Zimmermann, Ellen M; Hussain, Hero K
MR enterography has an established role in evaluating patients with Crohn disease providing essential complementary information to clinical assessment, and as an indispensible adjunct to clinical tools such as colonoscopy. MR enterography examinations can establish the diagnosis of Crohn disease, evaluate disease activity and complications, and assess treatment response, thus providing support for clinical decision-making. Currently, MR imaging findings are highly predictive of tissue inflammation and can be used clinically to guide clinical care.
Goldstein, N S; Sanford, W W; Bodzin, J H
Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become an established surgical procedure for ulcerative colitis. Occasional patients who have undergone IPAA develop persistent or recurrent episodes of pouchitis (chronic pouchitis), from which a subset also develop gastrointestinal and systemic complications that are identical to those seen in Crohn's disease. These complications include enteric stenoses or fistulas in the pouch or pouch inlet segment, perianal fistulas or abscesses, pouch fistulas, arthritis, iridocyclitis, and pyoderma gangrenosum. The development of Crohn's-like gastrointestinal complications in a patient with chronic pouchitis frequently engenders concern that the pathologist misinterpreted the proctocolectomy specimen as ulcerative colitis instead of Crohn's disease. We describe eight patients who developed chronic pouchitis and Crohn's-like complications after IPAA and total proctocolectomy. In each case, concern was voiced about misinterpretation of the proctocolectomy specimen as ulcerative colitis instead of Crohn's disease after the development of the Crohn's-like complications. Preoperatively, all eight patients had characteristic clinical, radiographic, and pathologic features of ulcerative colitis. Review of the pathology specimens indicated that all eight had ulcerative colitis. Crohn's-like complications are most likely related to chronic pouchitis, which probably is a form of recrudescent ulcerative colitis within the novel environment of the pouch. A diagnosis of Crohn's disease after IPAA surgery should only be made when reexamination of the original proctocolectomy specimen shows typical pathologic features of Crohn's disease, Crohn's disease arises in parts of the gastrointestinal tract distant from the pouch, pouch biopsies contain active enteritis with granulomas, or excised pouches show the characteristic features of Crohn's disease, including granulomas. There were no histologic differences in the total
Rubio, Carlos A; Villnow, Elizabeth; Sundelin, Birgitta; Eriksson, Elina; Dolapcsiev, Karoli; Björk, Jan; Befrits, Ragnar; Tengvar, Magnus; Iversen, Henrik
Fabry disease is an inherited (X-linked) lysosomal storage disorder caused by deficiency of α-galactosidase A, leading to accumulation of globotriaosylceramide in various tissues. A 57-year-old male with a family history and laboratory findings of Fabry disease, was consulted for severe abdominal pain, undulating pyrexia, weight loss and diarrhea. The tentative clinical diagnosis of Crohn's ileitis was supported at computed tomographic examination, at laparotomy and at inspection of the resected ileal segment. Histology revealed chronic and acute inflammation, thick-walled occluded vessels, fibrosis and characteristic bi-refringent lamellar deposits of globotriaosylceramide and calcifications. Multi-nucleated giant cells contained phagocytized bi-refringent material. Transmission electron microscopy showed cells with irregular cytoplasmic bodies displaying distinctive zebra-like lamellar structures. It is submitted that the gastrointestinal phenotype of Fabry disease may concur with symptoms resembling abdominal Crohn's disease.
Lee, So Mi; Choi, Young Hun
Crohn's disease is a chronic idiopathic inflammatory disease of the intestines characterized by frequent relapse and remission. It often develops in children and adolescents, who are vulnerable to repeated exposure to ionizing radiations. Magnetic resonance enterography (MRE) is an increasingly important radiation-free imaging modality that is used to evaluate pediatric patients with Crohn's disease. MRE can evaluate extraluminal and extraintestinal abnormalities as well as the status of the bowel wall. In addition, MRE has an advantage in the evaluation of the small bowel involvement. MRE can be used for the initial diagnosis of Crohn's disease, and can aid in the assessment of disease activity and complications such as penetrating and fibrostenotic diseases. The aims of this article are to review the MRE technique for obtaining diagnostic and high-quality images and to discuss interpretations of imaging findings in patients with Crohn's disease. PMID:26473134
Yokoyama, Yoko; Fukunaga, Ken; Kamikozuru, Koji; Sato, Toshiyuki; Kawai, Mikio; Nogami, Koji; Nagase, Kazuko; Nakamura, Misaki; Immured, Masaki; Hida, Nobuyuki; Nakamura, Shiro
In patients with inflammatory bowel disease infected with hepatitis B virus (HBV), immunosuppressive therapy required to suppress active inflammatory bowel disease may promote HBV reactivation. A 27-year-old corticosteroid-naive woman with Crohn's disease (CD) activity index of 249.8 complicated by HBV infection was offered Entecavir to control HBV reactivation during immunosuppressive therapy for CD. The patient refused Entecavir, fearing that it might adversely affect her pregnancy outcome. Instead, we applied intensive granulocyte/monocyte adsorptive apheresis (GMA) at two sessions per week to deplete inflammatory cytokine-producing leucocytes as an immunosuppressive therapy in this case. GMA induced stable remission (CD activity index, I 105) and endoscopic improvement without HBV reactivation or safety concern. Furthermore, CD remission was paralleled by suppression of tumor necrosis factor and interleukin as measured in serum samples. Immunosuppressive therapy required to treat an active CD potentially can promote HBV reactivation and worsen liver function. In this study involving a CD case complicated by chronic HBV infection, intensive GMA as a non-pharmacologic treatment intervention was associated with clinical remission and endoscopic improvement without HBV reactivation. Furthermore, GMA was well-tolerated and was without any safety concern. However, suppression of tumor necrosis and interleukin-6by GMA in this clinical setting is potentially very interesting. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
Chamaillard, Mathias; Cesaro, Annabelle; Lober, Pierre-Emmanuel; Hober, Didier
Although a causing viral infectious agent remains untraceable in Crohn's disease, most recent genome-wide association studies have linked the FUT2 W143X mutation (resulting in asymptomatic norovirus infection) with the pathogenesis of Crohn's ileitis and with vitamin B12 deficiency (i.e., a known risk factor for Crohn's disease with ileal involvement). In line with these findings, host variations in additional genes involved in host response to norovirus infection (such as ATG16L1 and NOD2) predispose humans to Crohn's ileitis. One may therefore presume that asymptomatic norovirus infection may contribute to disruption of the stability of the gut microbiota leading to Crohn's ileitis. These paradigms highlight not only the need to revisit the potential transmissibility of Crohn's disease, but also potential safety issues of forthcoming clinical trials on human probiotic infusions in Crohn's ileitis by rigorous donors screening program.
Fidder, Herma H; Chowers, Yehuda; Lidar, Merav; Sternberg, Matan; Langevitz, Pnina; Livneh, Avi
Crohn disease and familial Mediterranean fever (FMF) are inflammatory diseases characterized by abdominal pain and fever. The concurrence of the 2 diseases (FMF-CD) may pose a challenge to diagnosis and treatment. We undertook the present study to determine the prevalence of Crohn disease in FMF and to characterize FMF-CD patients clinically and genetically. Using a computerized search, the patients of our FMF clinic were screened for a concomitant diagnosis of Crohn disease. Patients and their medical records were thoroughly examined, and their DNA was genotyped for mutations in the MEFV gene. Control groups of ethnically and sex-matched patients suffering from each of the diseases alone, either Crohn disease or FMF, were used for comparison. We identified 7 patients with concomitant Crohn disease and FMF, which is more than the expected prevalence in the general population (p = 0.03). Crohn disease presented at a significantly later age in the FMF-CD group (40.6 +/- 10.0 yr versus 26.2 +/- 11.4 yr; p < 0.004). Disease severity and other characteristics of Crohn disease were comparable to the Crohn disease control group. Contrary to the FMF control group patients, FMF in FMF-CD patients was characterized by a higher attack frequency (p < 0.05) and increased prevalence of amyloidosis (p < 0.02). The overall severity score was similar in both groups. In conclusion, Crohn disease appears to be more prevalent in FMF and presents later than in patients without FMF. FMF in this group of patients shows a higher attack frequency and is more often complicated by amyloidosis.
Prasad, Meena A.; Lo, Amy; Bellaguarda, Emanuelle; Strong, Scott; Hanauer, Stephen B.
Although Crohn's disease has been associated with an increased risk of small bowel adenocarcinoma, primary adenocarcinoma arising from an ileostomy is a complication that has been rarely documented in Crohn's disease. Chronic small bowel inflammation may lead to development of malignancy through the dysplasia-carcinoma sequence. We report a case of a 61-year-old woman with Crohn's ileocolitis diagnosed with a primary adenocarcinoma at the ileostomy with metastases to the liver 47 years after proctocolectomy, and review the literature. PMID:27622191
Rhee, Sung-Min; Park, Ki Jeong
Numerous causes of hypertrophic osteoarthropathy (HOA) have been reported. Commonly, secondary osteoarthropathy accompanies pulmonary diseases such as carcinoma of the lung, pleural tumors, lung abscesses, and bronchiectasis. However, HOA in inflammatory bowel disease is a rare complication. There are only a few reports of secondary HOA with Crohn's disease. Our purpose was to report another case of HOA in Crohn's disease. We describe a case of a 27-year-old man with underlying Crohn's disease presenting with 2 years of pain in multiple joints. Radiographic findings suggested HOA in extremities. We performed a conservative treatment including medication and rehabilitations. The patient's symptoms were much improved at the latest follow-up. Although numerous studies on HOA have been published, the pathogenesis of HOA is still unclear. Various treatment modalities were recommended but further studies to uncover the pathogenesis of HOA with Crohn's disease and to establish a treatment modality are needed. PMID:25025001
Malcolm, A; Prather, C M
Angioedema usually presents as episodic attacks of swelling of the face, airway and extremities, but it may also involve visceral tissues. A 58-year-old woman with repeated episodes of abdominal pain, nausea and vomiting had two laparotomies and was treated for Crohn's disease for two years before a diagnosis of acquired intestinal angioedema was made. This case provides important insights into the presentation of intestinal angioedema.
Gontijo, João Renato Vianna; Leidenz, Franciele Antonieta Bianchi; de Sousa, Maria Silvia Laborne Alves
Metastatic Crohn's disease is a rare skin manifestation, defined by granulomatous skin lesions that are discontinuous to the affected gastrointestinal tract and histopathologically resembling inflammatory bowel lesions. Up to 44% of patients with Crohn's disease have cutaneous manifestations, of which metastatic lesions are the least common. We present a case of an adolescent with refractory Crohn's disease and persistent papules and plaques on the skin. PMID:27579756
Roediger, W E W
Intestinal diversion with reconnection in active Crohn's disease (CD) indicates that luminal contents or bacteria contribute to the formation of CD lesions. Fluorescent staining for mycoplasma in freshly resected Crohn's tissue and electron microscopy reveal intracellular organisms akin to mycoplasma. Historically, tissue culture of CD has shown mycoplasma described as contaminants. Mycoplasma are surface epithelial parasites requiring exogenous cholesterol for membrane stability and cell entry. PCR of intestinal tissue has shown Mycoplasma pneumoniae to be detectable more significantly in CD. Oral M. iowae in experimental poultry localizes to the distal small bowel and colon. Hypothetically, lipopeptides of mycoplasmal membranes are proposed to cause chronicity and stronger immune responses than by other bacteria. 'Intestinal' mycoplasmas, from a number of observations, deserve consideration as organisms mediating inflammation of acute and chronic CD.
[The role of nutritional status on serum immunoglobulins, body weight and postoperative infectious-related complications in patients with Crohn's disease receiving perioperative parenteral nutrition].
Yao, Guo-xiang; Wang, Xiu-rong; Jiang, Zhu-ming; Zhang, Si-yuan; Ma, En-ling; Ni, An-ping
To evaluate the role of nutritional status on serum immunoglobulins, body weight and postoperative infectious-related complications in patients with Crohn's disease receiving perioperative parenteral nutrition (PN). 32 patients with Crohn's disease receiving perioperative parenteral nutrition in our department between 1984 and 1994 were enrolled in this survey. 16 patients with loss of body weight in the range of 15%-30% were assigned to the malnutrition group, the other 16 patients with normal weight or loss of body weight less than 15% to the control group. Serum IgM, IgG and IgA levels were measured before and after PN by enzyme-linked immunosorbent assays. Liver function, body weight changes and postoperative complications were also analyzed. IgM levels were elevated before PN in both groups [control group: (133 +/- 16) mg/dl, malnutrition group: (139 +/- 41) mg/dl; normal value: (110 +/- 35) mg/dl; P = 0.04], decreased to normal value [(105 +/- 29) mg/dl, P = 0.02] in the malnutrition group while having no obvious changes in the control group [(129 +/- 13) mg/dl, P = 0.34]. No significant changes in concentrations of IgG and IgA were found (P in the range of 0.20-0.57). The average weight gain was 1.862 kg in malnutrition group [before PN: (45.8 +/- 8.9) kg, after PN: (48.0 +/- 8.8) kg; P = 0.005] and no significant changes in the control group [before PN: (55.6 +/- 6.1) kg, after PN: (56.3 +/- 6.0) kg; P = 0.46]. There was an increase in infectious complications in the control group (control group: 4 cases, 25%, malnourished group: 2 cases, 12.5%; P = 0.13). Perioperative parenteral nutrition ameliorated the humoral immunity, increased the body weight in patients with obvious malnutrition, whereas it had little value for those without or with mild malnutrition.
Feurle, G E; Keller, O; Hassels, K; Jesdinsky, H J
Impairment of social function was measured by questionnaire in 270 patients with Crohn's disease. In about half of them, the disease had had its onset below the age of 20 years. In 10%, schooling or job training was delayed or even had to be abandoned. Ten percent of the patients were forced to change their occupation because of the disease. 23.5% of the patients stated that their illness had prevented them from having whole-day jobs. Ten percent had temporary or permanent pensions; 3.8% were unemployed. 43.7% of patients stated that the relation to their family and (or) partner was impaired by the disease; in 36.4% the disease had interfered with leisure time activities. The results show that Crohn's disease has social effects which in the individual case can be very serious; they correlate with the duration and severity of the disease. Nonetheless, the majority of patients succeeds in mastering their chosen training and occupation and leading an active life.
Tonkić, Ante; Borzan, Vladimir
The treatment of fistulating Crohn's disease should include a combined medical and surgical approach and should be defined on an individual basis. Asymptomatic enteroenteric fistulas usually require no treatment, but internal fistulas (gastrocolic, duodenocolic, enterovesical) that cause severe or persistent symptoms require surgical intervention. While low asymptomatic anal-introital fistula may not need surgical treatment, in case of a symptomatic enterovaginal fistula surgery is usually required. There are no controlled-randomized trials to assess the effect of medical treatment for non-perianal fistulating Crohn's disease. The incidence of perianal fistulae varies according to the location of the disease, with its occurrence varying between 21-23%. The diagnostic approach should include an examination under anesthesia, endoscopy, and either MRI or EUS before the treatment begins. Asymptomatic simple perianal fistulas require no treatment. The presence of a perianal abscess should be ascertained and if present should be drained urgently. In case of a complex perianal disease, seton placement should also be recommended. Antibiotics (metronidazole and ciprofloxacine) are useful for treating complex perianal disease, however, when discontinued, most of the fistulas relapse. The current consensus suggests that azathioprine/6-mercaptopurine is the first line medical therapy for complex perianal disease, which is always given in combination with surgical therapy (seton, fistulotomy/fistulectomy). Anti TNF-alpha agents (infliximab and adalimumab) should be used as a second choice medical treatment. In refractory and extensive complex perianal disease a diverting stoma or proctectomy should be performed.
Patel, Ashish S; Suarez, Lisbet D; Rosh, Joel R
Adalimumab, a human monoclonal antibody to tumor necrosis factor alpha (TNF-α), was initially approved for the treatment of moderate to severe rheumatoid arthritis in 2002. In the subsequent years, its anti-inflammatory properties were applied to the treatment of psoriatic arthritis, ankylosing spondylitis, adult Crohn's disease (CD), plaque psoriasis, polyarticular juvenile idiopathic arthritis, adult ulcerative colitis and most recently in 2014, pediatric CD. The biologic era in pediatric CD has changed and redefined the therapeutic approach to this challenging lifelong disease. This article summarizes the clinical legacy of adalimumab with a focus on its most recent expanded indication, pediatric CD.
Ignatova, Simone; Ekstedt, Mattias
We here report a case of a young man who presented to his general practitioner with diarrhea. Inflammatory bowel disease was suspected and a colonoscopy showed aphthous lesions suggestive of Crohns' disease but biopsies revealed eggs of Enterobius vermicularis. When treated for this parasite, his symptoms were alleviated and a followup colonoscopy revealed a normal colon and distal ileum. Enterobius vermicularis is the most common parasite worldwide and has been attributed with many different presentations and pathologies. It is therefore necessary to maintain vigilance, even in high-income countries, in order to diagnose patients with one of the many atypical presentations of pinworms. PMID:23555063
Moret, Inés; Cerrillo, Elena; Navarro-Puche, Ana; Iborra, Marisa; Rausell, Francisco; Tortosa, Luis; Beltrán, Belén
Crohn's disease (CD) is characterized by transmural inflammation that is most frequently located in the region of the terminal ileum. Although the physiopathological mechanisms of the disease are not yet well defined, the unregulated immune response is associated with high production of reactive oxygen species (ROS). These elements are associated with complex systems known as antioxidant defenses, whose function is ROS regulation, thereby preventing the harmful effects of these elements. However, the presence of an imbalance between ROS production and ROS elimination by antioxidants has been widely described and leads to oxidative stress. In this article, we describe the most significant findings on oxidative stress in the intestinal mucosa and peripheral blood.
Lightner, Amy L; Pemberton, John H; Loftus, Edward J
Crohn's disease (CD) of the pouch is an increasingly recognized diagnosis after ileal pouch-anal anastomosis. This post-ileal pouch-anal anastomosis diagnosis in conjunction with pouchitis remains the leading reason for pouch excision. Unfortunately, CD of the pouch remains a difficult diagnosis with lack of a uniform definition largely because of its similarity to common postoperative pouch complications, including pouchitis, abscess formation, or stricture at the anastomosis. Once diagnosed, treatment algorithms largely include multimodal therapy including biologics. This review focuses on the definition, etiology, diagnosis, and treatment for CD of the pouch, a postoperative de novo diagnosis of CD.
Kim, David H; Carucci, Laura R; Baker, Mark E; Cash, Brooks D; Dillman, Jonathan R; Feig, Barry W; Fowler, Kathryn J; Gage, Kenneth L; Noto, Richard B; Smith, Martin P; Yaghmai, Vahid; Yee, Judy; Lalani, Tasneem
Crohn disease is a chronic inflammatory disorder involving the gastrointestinal tract, characterized by episodic flares and times of remission. Underlying structural damage occurs progressively, with recurrent bouts of inflammation. The diagnosis and management of this disease process is dependent on several clinical, laboratory, imaging, endoscopic, and histologic factors. In recent years, with the maturation of CT enterography, and MR enterography, imaging has played an increasingly important role in relation to Crohn Disease. In addition to these specialized examination modalities, ultrasound and routine CT have potential uses. Fluoroscopy, radiography, and nuclear medicine may be less beneficial depending on the clinical scenario. The imaging modality best suited to evaluating this disease may change, depending on the target population, severity of presentation, and specific clinical situation. This document presents seven clinical scenarios (variants) in both the adult and pediatric populations and rates the appropriateness of the available imaging options. They are summarized in a consolidated table, and the underlying rationale and supporting literature are presented in the accompanying narrative. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
Botti, Fiorenzo; Caprioli, Flavio; Pettinari, Diego; Carrara, Alberto; Magarotto, Andrea; Contessini Avesani, Ettore
Surgery is well-established option for the treatment of Crohn's disease that is refractory to medical therapy and for complications of the disease, including strictures, fistulas, abscesses, bleeding that cannot be controlled endoscopically, and neoplastic degeneration. For a condition like Crohn's disease, where medical management is the rule, other indications for surgery are considered controversial, because the therapeutic effects of surgery are limited to the resolution of complications and the rate of recurrence is high, especially at sites of the surgical anastomosis. In the authors' opinion, however, surgery should not be considered a last-resort treatment: in a variety of situations, it should be regarded as an appropriate solution for managing this disease. Based on a review of the literature and their own experience, the authors examine some of the possibilities for surgical interventions in Crohn's disease and the roles played in these cases by diagnostic imaging modalities.
Bassas-Vila, J; González Lama, Y
The first description of perianal fistulas and complications in Crohn disease was made 75 years ago by Penner and Crohn. Published studies have subsequently confirmed that perianal fistulas are the most common manifestations of fistulising Crohn disease. Hidradenitis suppurativa was described in 1854 by a French surgeon, Aristide Verneuil. It is a chronic, inflammatory, recurrent and debilitating disease of the pilosebaceous follicle, that usually manifests after puberty with deep, painful and inflamed lesions in the areas of the body with apocrine glands, usually the axillary, inguinal and anogenital regions. The differential diagnosis between hidradenitis suppurativa and Crohn disease can be challenging, especially when the disease is primarily perianal. When they occur simultaneously, hidradenitis suppurativa and Crohn disease show severe phenotypes and patients can respond to anti-tumour necrosis factor therapy, although adalimumab is currently the only treatment with demonstrated efficacy in hidradenitis suppurativa and Crohn disease. In addition, there is sometimes a need for different complementary surgical procedures. Copyright © 2016 Elsevier España, S.L.U. y AEDV. All rights reserved.
Sides, Cleve; Trinidad, Mari Charisse; Heitlinger, Leo; Anasti, James
Although Crohn disease (CD) is considered an inflammatory bowel disease, extraintestinal gynecologic manifestations are varied, frequent, and oftentimes difficult to manage. Its predilection for young and reproductive-age women makes it an important disease process for the gynecologist to understand, as its complications can have long-term repercussions on the developmental, sexual, reproductive, and psychological health of affected women. Patients may present with a variety of vulvovaginal, perineal, perianal, and urologic complaints. Perianal involvement from an intestinal fistula is the most common skin manifestation seen in CD. Other gynecologic manifestations include metastatic CD and rectovaginal and urovaginal fistulas. Recognition and accurate diagnosis of extraintestinal gynecologic manifestations, as well as a good understanding of the gynecologic effects of chronic disease, are necessary for optimal management. The article provides an overview of CD and highlights the gynecologic considerations in caring for women affected by this disease.
Cottone, Mario; Orlando, Ambrogio; Renna, Sara
Increased understanding of the biological mechanisms of Crohn's disease has opened the door to a large number of new molecules; some of these are approved for clinical use, while others remain under evaluation. In this review, we examine the clinical efficacy of all the new drugs that have been evaluated in controlled trials in the last 12 years. Anti-TNF therapy has been reviewed briefly, given the many comprehensive reviews on this topic; attention is focused mainly on the other biological therapies. In assessing the clinical efficacy of these molecules, we consider only the remission rate, as this is considered the most meaningful end point in clinical practice. We analyzed the main biological mechanisms of Crohn's disease and the new drugs whose use is based on insights into these mechanisms. We reviewed the following new drugs: probiotics, GM-CSF, IL-10, IL-11, anti-IL-6, anti-IL-12/-23, everolimus, anti-IFN-γ, IFN-β-I, co-stimulators, anti-integrins, anti-intercellular adhesion molecule 1, small molecules and mitogen-activated protein kinase inhibitors. Anti-TNF therapies remain the best options, followed by anti-integrin drugs. The most promising new therapies are anti-IL-23, but further data are necessary. The disappointing results with other molecules may depend on the quality of trials and possibly on inadequate dosage of the drug.
Harb, William J
There is no cure for Crohn disease. Newer treatments, such as biological therapy, have led to an improved quality of life. This article focuses on the surgical management of Crohn disease of the colon, rectum, and anus. Restorative and nonrestorative surgical options for colonic Crohn disease are discussed. Treatment options for perianal Crohn disease are also reviewed.
Korzenik, J R
The understanding of the pathophysiology of Crohn's disease is currently undergoing a reassessment. The concept of this disease as a primary T cell disorder is being questioned, with a new emphasis on the role of innate immunity in initiating early events and in perpetuating the inflammatory state. Crohn's disease has been proposed instead to result from impaired innate immunity, encompassing the mucosal barrier and cellular elements including neutrophils and macrophages. Recent advances in genetics, functional studies on innate immunity and therapeutic trials on patients with Crohn's disease have lent support to this evolving hypothesis. PMID:17172582
Cahill, Caitlin; Gordon, Philip H; Petrucci, Andrea; Boutros, Marylise
This review of the literature on small bowel carcinoma associated with Crohn's disease specifically addresses the incidence, risk factors, and protective factors which have been identified. It also reviews the clinical presentation, the current modalities of diagnosis, the pathology, treatment, and surveillance. Finally, the prognosis and future direction are addressed. Our experience with small bowel adenocarcinoma in Crohn's disease is reported. Readers will be provided with a better understanding of this rare and often poorly recognized complication of Crohn's disease.
Yeung, Vincent; Govind, Anusha G; Arastu, Sanaa; Henry, Christopher H
We report a 63-year-old woman who presented with 1 month of non-productive cough and non-bloody diarrhea. She was on maintenance therapy for a 15-year history of Crohn's disease. Treatment with systemic corticosteroids resulted in rapid improvement of both her diarrhea and respiratory symptoms. Our patient is unique in that she presented with tracheobronchitis during an acute flare of her Crohn's without obvious lung pathology on chest imaging. Tracheobronchitis is a rare manifestation of inflammatory bowel disease that should be considered in Crohn's disease patients presenting with persistent non-infectious cough.
Wright, Emily K; Novak, Kerri L; Lu, Cathy; Panaccione, Remo; Ghosh, Subrata; Wilson, Stephanie R
Aims of treatment for Crohn disease have moved beyond the resolution of clinical symptoms to objective end points including endoscopic and radiological normality. Regular re-evaluation of disease status to safely, readily and reliably detect the presence of inflammation and complications is paramount. Improvements in sonographic technology over recent years have facilitated a growing enthusiasm among radiologists and gastroenterologists in the use of ultrasound for the assessment of inflammatory bowel disease. Transabdominal intestinal ultrasound is accurate, affordable and safe for the assessment of luminal inflammation and complications in Crohn disease, and can be performed with or without the use of intravenous contrast enhancement. Perianal fistulizing disease is a common, complex and often treatment-refractory complication of Crohn disease, which requires regular radiological monitoring. Endoanal ultrasound is invasive, uncomfortable and yields limited assessment of the perineal region. Although magnetic resonance imaging of the pelvis is established, timely access may be a problem. Transperineal ultrasound has been described in small studies, and is an accurate, painless and cost-effective method for documenting perianal fluid collections, fistulas and sinus tracts. In the present article, the authors review the literature regarding perineal ultrasound for the assessment of perianal Crohn disease and use case examples to illustrate its clinical utility.
Papadakis, Konstantinos A
Crohn's disease is a chronic inflammatory intestinal disorder characterized by chronic, recurrent, often granulomatous inflammation affecting any part of the intestines, but most frequently involving the small bowel and colon. The development of novel biologic agents targeting tumor necrosis factor has revolutionized the treatment of patients with moderate-to-severe Crohn's disease. Adalimumab, a fully human anti-tumor necrosis factor monoclonal antibody, has recently been evaluated for Crohn's disease and was found to be effective for induction of clinical response and remission in patients with active inflammatory disease. Preliminary experience also indicates that adalimumab is useful in patients with prior intolerance or loss of response to infliximab. The rate of adverse events is comparable to other tumor necrosis factor antagonists in rheumatoid arthritis, but longer studies are needed to evaluate both the long-term efficacy and safety of adalimumab in the treatment of Crohn's disease.
Li, Y; Zhu, W M; Gong, J F; Guo, Z; Cao, L
To analyze the value of postoperative C-reactive protein (CRP) in predictive diagnosis of postoperative intra-abdominal septic complications (IASC) for patients with Crohn disease (CD). Clinical data of patients with CD received intestinal resection and anastomosis surgery at Research Institute of General Surgery, Jinling Hospital from January 2011 to January 2015 were analyzed. Patients were divided into two groups by whether suffer from IASC 1 month after surgery, including IASC group and no-IASC group. Propensity score matching method was used to match the general clinical data. A total of 54 patients were analyzed, including IASC 17 cases, no-IASC 37 cases. Postoperative CRP at 1-day and 3-day were compared between the two groups using t test. Receiver operator characteristic (ROC) cure was used to analyze the value of postoperative CRP in predictive diagnosis of IASC. IASC group had higher levels of CRP at 1-day ((78±13) mg/L vs. (54±19) mg/L, t=4.633, P=0.000) and 3-day ((103±19) mg/L vs. (69±21) mg/L, t=5.859, P=0.000) after surgery than no-IASC group. ROC analysis showed that the CRP 3-day after surgery cut-off point value of 81.45 mg/L, as used for the predictive diagnosis of IASC, provided a sensitivity of 94.1%, a specificity of 82.9%, an area under the curve of 0.90, better than CRP 1-day after surgery. Postoperative CRP can be used as a predictive diagnosis of IASC for CD patients received intestinal resection and anastomosis surgery.
Biancone, Livia; Tema, Giorgia; Porokhnavets, Kristina; Tesauro, Manfredi; Gaspari, Achille L.; Sica, Giuseppe S.
Midgut malrotation is an anomaly of fetal intestinal rotation. Its incidence in adults is rare. A case of midgut malrotation in a 51-year-old man with complicated Crohn's disease of the terminal ileum is presented. Symptoms, diagnosis, and treatment are reviewed. Preoperative workup led to correct surgical planning that ultimately allowed a successful laparoscopic resection. PMID:25419109
Shenoy-Bhangle, Anuradha; Gee, Michael S
Perianal penetrating complications of Crohn disease are among the most important causes of symptoms in the pediatric population. High-quality diagnostic imaging of the perianal region is crucial for treatment planning and therapeutic response assessment. MRI, with its absence of ionizing radiation and high soft-tissue resolution, provides an excellent noninvasive tool for evaluation of perianal fistulae and associated abscesses, as well as their anatomical relationship to the anal sphincter complex. In this review we discuss the role of MRI in initial diagnosis and follow-up of perianal fistulizing Crohn disease in the pediatric population.
Bona, D; Incarbone, R; Chella, B; Vecchi, M; Bonavina, L
Crohn's disease may affect any segment of the digestive tract, more commonly the distal ileum, colon and/or perianal region. There is an increasing number of reports dealing with foregut Crohn's disease. We present the case of a patient with a history of heartburn and multiple spontaneous perforations of the esophagus, duodenum and jejunum as a primary manifestation of Crohn's disease who required emergency surgical and endoscopic procedures. Early detection of Crohn's disease may decrease the incidence of acute life-threatening complications provided that appropriate medical treatment is administered and a multidisciplinary approach is offered to these patients.
Sobrado, Carlos Walter; Leal, Raquel Franco; Sobrado, Lucas Faraco
The main objectives of clinical therapy in Crohn's disease are clinical and endoscopic remission without the use of corticosteroids for long periods of time, prevention of hospitalization and surgery, and improvement of quality of life. The main limitation of drug therapy is the loss of response over the long term, which makes incorporation of new drugs to the therapeutic arsenal necessary. This review analyses the main drugs currently used in clinical treatment of Crohn's disease.
Rosmaninho, Aristóteles; Sanches, Madalena; Salgado, Marta; Alves, Rosário; Selores, Manuela
Crohn's disease is a multisystem chronic granulomatous inflammatory disease that primarily affects the gastrointestinal tract. In the majority of the cases, the cutaneous manifestations follow the intestinal disease, but occasionally dermatological lesions are the inaugural event and may constitute the only sign of the disease. Vulvoperineal involvement is rare, may precede bowel symptoms by months to years and may go unrecognized. Due to the paucity of reports of Crohn's disease at this location and in the absence of randomized trials, there are no standard treatments for the cutaneous disease. We describe the case of a 47 year-old woman with vulvoperineal Crohn's disease without digestive involvement, that was successfully managed with metronidazole. PMID:24346884
Hubbard, Vanessa M; Cadwell, Ken
The etiology of the intestinal disease Crohn's disease involves genetic factors as well as ill-defined environmental agents. Several genetic variants linked to this disease are associated with autophagy, a process that is critical for proper responses to viral infections. While a role for viruses in this disease remains speculative, accumulating evidence indicate that this possibility requires serious consideration. In this review, we will examine the three-way relationship between viruses, autophagy genes, and Crohn's disease and discuss how host-pathogen interactions can mediate complex inflammatory disorders.
Fiorino, Gionata; Peyrin-Biroulet, Laurent; Danese, Silvio
Crohn's disease leads to complications in the majority of patients on the long term. Strictures, fistulas and abscesses usually involve the bowel wall or extra-intestinal compartments, and conventional diagnostic tools, such as colonoscopy or barium studies, are not able to assess them. Magnetic resonance imaging has been proven to be accurate in detecting activity, severity and complications of Crohn's disease. Because of its reproducibility and safety, it can be considered the first-choice technique to complete Crohn's disease staging, and to monitor disease evolution. Recently, the concept of bowel damage has risen into the field of inflammatory bowel diseases. It has been shown that bowel damage induced by the disease can impact on patients' life, beyond intestinal symptoms. Data coming from rheumatology suggest that blockade of organ damage should be achieved independently from disease-related symptoms, and that a "damage driven" approach should be preferred than a "symptom-driven" one. This review of the literature aims to investigate the role of magnetic resonance imaging in assessing disease complications, which cause organ damage, and to explore future perspective in order to develop new therapeutical strategies and new tailored therapies, based on the prevention of intestinal damage.
Treitman, Adam; Tabriz, Muhammed
Purulent skeletal muscle abscesses can occur in Crohn's disease. We report a case of a sterile seroma complicating percutaneous drainage of a purulent skeletal muscle abscess in Crohn's ileitis. We compare and contrast this case with a similar case we published earlier. We emphasize the importance of recognition and differentiation from a septic purulent abscess. PMID:27529038
Philip, Sunu; Kamyab, Armin; Orfanou, Paraskevi
The surgical management of the complications of Crohn disease is often challenging. These difficulties are compounded in pregnancy by competing interests of the mother and the baby. In this report, we describe the presentation and surgical management of a patient in her second trimester with active Crohn disease who required emergent surgical intervention. She had presented with the uncommon complication of a free perforation in the presence of active untreated disease.
Chidi, Vivian N; Schwartz, David A
Perianal fistula is a complication of Crohn's disease that carries a high morbidity. It is a channel that develops between the lower rectum, anal canal and perianal or perineal skin. The development of perianal fistulas typically connotes a more aggressive disease phenotype and may warrant escalation of treatment to prevent poor outcomes over time. Based on fistula anatomy, debris can form inside these tracts and cause occlusion, which subsequently leads to abscess formation, fever and malaise. The clinical presentation is often with complaints of pain, continuous rectal drainage of fecal matter as well as malodorous discharge. Considering that the presence of fistulas often indicates refractory and aggressive disease, early identification of its presence is important. Some patients may not have the classic symptoms of fistulizing disease at presentation and others may have significant scarring and/or pain from previous fistulizing episodes, which can make an accurate assessment on physical exam alone problematic. As a result, utilizing diagnostic imaging is the best means of identifying the early signs of perianal fistulas or abscess formation in these patients. Several imaging modalities exist which can be used for diagnosis and management. Endoscopic ultrasound and pelvic MRI are considered the most useful in establishing the diagnosis. However, a combination of multiple imaging modalities and/or examination under anesthesia is probably the most ideal. Incomplete characterization of the fistula tract(s) extent or the presence of abscess carries a high morbidity and far-reaching personal expense for the patient - promoting worsening of the disease.
Extremely variable in their clinical expression, inflammatory bowl diseases evolve by flare-ups interspersed with phases of remission. Complications can be severe, sometimes requiring surgery. While treatments have evolved considerably, therapeutic patient education plays an important role in the therapeutic approach.
Smith, Sonny; Narayanan, Ram M.; Messaris, Evangelos
Crohn's disease is a condition that causes inflammation and associated complications along any section of the digestive tract. Over the years, numerous radiological and endoscopic methods as well as the use of ultrasound have been developed to examine and diagnose inflammatory bowel disorders such as Crohn's disease. While such techniques have much merit, an alternative medical solution that is safe, non-invasive, and inexpensive is proposed in this paper. Reflections from electromagnetic signals transmitted by an ultra-wide band (UWB) radar allow for not only range (or extent) information but also spectral analysis of a given target of interest. Moreover, the radar cross-section (RCS) of an object measures how detectable the electromagnetic return energy of such an object is to the radar. In the preliminary phase of research, we investigate how disparities in the dielectric properties of diseased versus non-diseased portions of the intestines can aid in the detection of Crohn's disease. RCS analysis from finite-difference time-domain (FDTD) method simulations using a simple 3D model of the intestines are presented. The ultimate goal of our research is to design a UWB radar system using a suitable waveform to detect and monitor Crohn's disease.
Gecse, Krisztina Barbara; Végh, Zsuzsanna; Lakatos, Péter László
Anti-TNF therapy has revolutionized the treatment of inflammatory bowel diseases, including both Crohn's disease and ulcerative colitis. However, a significant proportion of patients does not respond to anti-TNF agents or lose response over time. Recently, therapeutic drug monitoring has gained a major role in identifying the mechanism and management of loss of response. The aim of this review article is to summarize the predictors of efficacy and outcomes, the different mechanisms of anti-TNF/biological failure in Crohn's disease and identify strategies to optimize biological treatment.
Lemann, M; Messing, B; D'Agay, F; Modigliani, R
Symptomatic respiratory tract involvement with granulomatous bronchial lesions has not yet been described in Crohn's disease. We report two patients with colonic Crohn's disease and severe respiratory symptoms (dyspnoea associated in one of the patients with voicelessness); erythema, aphthoid and superficial ulcerations were found in the colon and whitish granulations in the bronchi at endoscopy. Non-caseating tuberculoid granulomas were found in the colonic mucosa of both patients, as well as in the bronchial mucosa of one of them; in the second a diffuse inflammatory infiltrate including epithelioid cells was found underneath an erosion of bronchial epithelium. Both patients improved on oral prednisone. These two patients probably had bronchial involvement by Crohn's disease. Images Figure PMID:3428695
Carranza, Dafnis C; Young, Lorraine
Metastatic Crohn's disease refers to cutaneous granulomatous lesions that are noncontiguous to the gastrointestinal tract. The treatment of cutaneous Crohn's disease is challenging. A patient with metastatic Crohn's disease whose lesions cleared after a 3-month course of cyclosporine is reported.
Timmermans, Sjoerd A.M.E.G.; Christiaans, Maarten H.L.; Abdul-Hamid, Myrurgia A.; Stifft, Frank; Damoiseaux, Jan G.M.C.; van Paassen, Pieter
Granulomatous interstitial nephritis has been observed in <1% of native renal biopsies. Here, we describe two patients with granulomatous interstitial nephritis in relation to Crohn's disease. Circulating helper and cytotoxic T cells were highly activated, and both cell types predominated in the interstitial infiltrate, indicating a cellular autoimmune response. After immunosuppressive treatment, renal function either improved or stabilized in both patients. In conclusion, granulomatous interstitial nephritis is a genuine extraintestinal manifestation of Crohn's disease, the treatment of which should include immunosuppressive agents. PMID:27478596
Yoon, Kichul; Chang, Kyu-Tae; Lee, Hong J.
Crohn's disease (CD) is a chronic inflammatory condition with relapsing-remitting behavior, often causing strictures or penetrating bowel damage. Its lifelong clinical course necessitates frequent assessment of disease activity and complications. Computed tomography (CT) enterography has been used as primary imaging modality; however, the concern for radiation hazard limits its use especially in younger population. Magnetic resonance (MR) imaging has advantages of avoiding radiation exposure, lower incidence of adverse events, ability to obtain dynamic information, and good soft-tissue resolution. MR enterography (MRE) with oral contrast agent has been used as primary MR imaging modality of CD with high sensitivity, specificity, and interobserver agreement. The extent of inflammation as well as transmural ulcers and fibrostenotic diseases can be detected with MRE. Novel MR techniques such as diffusion-weighted MRI (DWI), motility study, PET-MRI, and molecular imaging are currently investigated for further improvement of diagnosis and management of CD. MR spectroscopy is a remarkable molecular imaging tool to analyze metabolic profile of CD with human samples such as plasma, urine, or feces, as well as colonic mucosa itself. PMID:26413543
Patel, Kamal V; Darakhshan, Amir A; Griffin, Nyree; Williams, Andrew B; Sanderson, Jeremy D; Irving, Peter M
The majority of patients with Crohn's disease require abdominal surgery during their lifetime, some of whom will require multiple operations. Postoperative complications are seen more frequently in patients requiring abdominal surgery for Crohn's disease than in patients requiring abdominal surgery for other conditions. In this article, we review the evidence supporting preoperative optimization, discussing strategies that potentially improve surgical outcomes and reduce perioperative morbidity and mortality. We discuss the roles of adequate cross-sectional imaging, nutritional optimization, appropriate adjustments of medical therapy, management of preoperative abscesses and phlegmons, smoking cessation and thromboembolic prophylaxis. We also review operation-related factors, and discuss their potential implications with respect to postoperative complications. Overall, the literature suggests that preoperative management has a major effect on postoperative outcomes.
Feitosa, Marley Ribeiro; Féres Filho, Omar; Tamaki, Camila Mussolin; Perazzoli, Camila; Bernardes, Mário Vinícius Angelete Alvarez; Parra, Rogério Serafim; Rocha, José Joaquim Ribeiro da; Féres, Omar
To investigate de adjunctive effect of Hyperbaric Oxygen Therapy in a group of patients with refractory Crohn's disease. A total of 29 subjects with refractory Crohn's disease were submitted to daily sessions of Hyperbaric Oxygen Therapy, in a 2800 Sechrist Monoplace Hyperbaric Chamber (Sechrist, USA) pressurized to 2.4 ATA. Each session lasted 2 hours. The endpoint was closure of enterocutaneous fistulas and complete healing of Pyoderma Gangrenosum and perineal Crohn's disease. A total of 829 HBOT sessions were performed and no complications were noted. Overall success rate was 76% (22 cases). Pyoderma Gangrenosum and enterocutaneous fistulas had the highest successful healing rates (100% and 91%, respectively). Perineal Crohn's disease healing rate was 65%. Adjunctive Hyperbaric Oxygen Therapy promoted satisfactory healing in a group of patients with refractory Crohn's disease.
Ferguson, Lynnette R
Crohn's disease is a chronic relapsing condition that has no certain cure. Both genetic susceptibility and nutrition have key roles, but their level of involvement varies between patients. Interacting gene pathways influence the probability of disease development, but these are affected by stress and various environmental factors, including diet. In addition, the role of the gut microbiome must not be underestimated, as it is substantially altered in patients with Crohn's disease. Although an elemental diet might lead to disease remission, reintroducing real foods and sustainable diets in patients with Crohn's disease is currently difficult, and would benefit from the sensitivity and rapid feedback provided by the field of nutrigenomics. Nutrigenomics utilizes high-throughput genomics technologies to reveal changes in gene and protein expression that are modulated by the patient's nutrition. The most widely used technique thus far is transcriptomics, which permits measurement of changes in the expression of thousands of genes simultaneously in one sample. Given the volume of numbers generated in such studies, data-basing and bioinformatics are essential to ensure the correct application of nutrigenomics at the population level. These methods have been successfully applied to animal models of Crohn's disease, and the time is right to move them to human studies.
Colletti, Richard B; Baldassano, Robert N; Milov, David E; Margolis, Peter A; Bousvaros, Athos; Crandall, Wallace V; Crissinger, Karen D; D'Amico, Michael A; Day, Andrew S; Denson, Lee A; Dubinsky, Marla; Ebach, Dawn R; Hoffenberg, Edward J; Kader, Howard A; Keljo, David J; Leibowitz, Ian H; Mamula, Petar; Pfefferkorn, Marian D; Qureshi, M Azim
Variation in medical care can be a barrier to improving clinical outcomes. We aim to describe the variation in care of Crohn disease as provided by a broad sample of pediatric gastroenterologists. Two hundred forty-six Crohn disease patients of 93 pediatric gastroenterologists from 48 practice sites starting treatment with either thiopurine or infliximab were studied. We assessed variation in diagnostic testing that had been performed to establish the diagnosis of Crohn disease and to assess the phenotype, extent, and severity of disease. We also assessed variation in initial thiopurine and infliximab dosage and in nutritional therapy. Diagnostic studies in which care was uniform included complete blood count, performed in 100% of patients, erythrocyte sedimentation rate and colonoscopy in 96%, and upper endoscopy in 89%. However, imaging of the small bowel had not been performed in 19%, and a stool test for pathogens had not been performed in 29%. Thiopurine methyltransferase (TPMT) had been measured in 61% of patients before treatment with a thiopurine; in 85%, TPMT was normal. Nonetheless, even when TPMT was normal, 40% of patients received an initial dose of thiopurine that was lower than recommended. Testing for tuberculosis before initiating treatment with infliximab was not performed in 30%. In addition, 36% of severely underweight patients were not receiving a multivitamin supplement, supplemental formula, or tube feeding. There is variation in diagnostic and therapeutic interventions in the management of pediatric Crohn disease, and gaps exist between recommended and actual care.
Nagpal, Swati; Acharya, Anirudh B; Thakur, Srinath L
Crohn's disease (CD) is an inflammatory bowel disease with oral findings, including periodontal manifestations. Anemias, such as iron deficiency and anemia of chronic disease (ACD), are the most common hematologic complications of CD. Periodontitis has systemic effects, and may tend toward anemia, which can be explained by depressed erythropoiesis. In the report presented here, the authors review a case of Crohn's disease diagnosed 10 years previous to the patient presenting with a changing anemic profile and periodontal disease. A discussion of patient and disease management is included.
Białecki, Marcin; Białecka, Agnieszka; Laskowska, Katarzyna; Liebert, Ariel; Kłopocka, Maria; Serafin, Zbigniew
The chronic nature of Crohn's disease (CD) implicates necessity of multiple control assessments throughout patient's life. It is accepted that in patients with CD requiring disease monitoring, magnetic resonance enterography (MRE) and computed tomography enterography (CTE) are--apart from endoscopy--imaging studies of first choice. In practice, diagnostic imaging of patients with CD is troublesome, since MRE is an expensive and complicated study, and CTE exposes patients to high doses of ionizing radiation. Therefore, there is a need for new, both non-invasive and effective, methods of imaging in CD. Contrast-Enhanced Ultrasonography (CEUS) is a relatively new method using gas-filled microbubbles serving as contrast agent. It allows for detailed assessment of blood perfusion within intestine wall and peri-intestinal tissues, which enables detection and monitoring of inflammation and its qualitative assessment. The purpose of this paper is to describe CEUS examination technique and its clinical applications in patients with Crohn's disease.
Delgado, Montserrat G; Vega, Juan; Santamarta, Elena; Caminal, Luis
Few cases of Crohn's disease complicated with meningitis and epidural abscess have been described in literature. We present a case of a 42-year-old former smoker female patient diagnosed with Crohn's disease in September 1995 (with severe nutritional problems). On 20 February 2012, she was admitted due to a probable sepsis (without any previous treatment). After several days she developed a confusion syndrome (probable Wernicke's disease). On 5 March 2012, the patient presented with a febrile episode of 39 ° C. Two days later, the patient presented aphasia and paraparesis, and 3 days later she presented a complex partial status epilepticus. A lumbar puncture was performed and showed 131 leucocytes (63% granulocytes) and proteins 296.3. The abdominopelvic CT scan revealed a presacral collection that seem to extend cranially towards the lumbosacral spine. The lumbar MRI confirmed the lumbar epidural abscess secondary to the fistulisation of the presacral abscess.
Futami, Kitaro; Higashi, Daijiro; Hirano, Yukiko; Ikeda, Yuichi; Mikami, Koji; Hirano, Kimikazu; Miyake, Toru; Takahashi, Hiroyuki; Maekawa, Takafumi
Perianal lesions are a frequent complication of Crohn's disease (CD) and include fistula, abscess, anal ulcer, skin tag, anal stricture, and carcinoma. Perianal fistula is the most commonly observed condition and exhibits multiple incidence and intractable characteristics. The starting point for the management of perianal fistula is an accurate diagnosis, which requires careful exploration during an EUA. The condition is treated with medications such as antibiotics, immunosuppressants, or anti-tumor necrosis factor agents. However, it is difficult to maintain long-term remission. Surgical therapy is selected according to the type of fistula and can include conventional fistulotomy, seton drainage, diverting stoma, and anorectal amputation. After fistulotomy, recurrence is frequent and there is an increased risk of incontinence. Seton drainage is the preferred treatment to improve symptoms and preserve anal function. Stoma is useful to relieve symptoms but difficult to indicate for young patients. The optimum treatment for perianal fistula associated with CD remains controversial. Currently, the goal of therapy for these patients has shifted from complete fistula closure to reducing drainage from the fistula to improve their quality of life. Ongoing careful management is important to control anal symptoms and maintain long-term anal function in the treatment of patients with CD, while monitoring them to detect possible progression to anorectal carcinoma.
De Greef, E; Mahachie John, J M; Hoffman, I; Smets, F; Van Biervliet, S; Scaillon, M; Hauser, B; Paquot, I; Alliet, P; Arts, W; Dewit, O; Peeters, H; Baert, F; D'Haens, G; Rahier, J F; Etienne, I; Bauraind, O; Van Gossum, A; Vermeire, S; Fontaine, F; Muls, V; Louis, E; Van de Mierop, F; Coche, J C; Van Steen, K; Veereman, G
A Belgian registry for pediatric Crohn's disease, BELCRO, was created. This first report aims at describing disease presentation and phenotype and determining associations between variables at diagnosis and registration in the database. Through a collaborative network, children with previously established Crohn's disease and newly diagnosed children and adolescents (under 18 y of age) were recruited over a 2 year period. Data were collected by 23 centers and entered in a database. Statistical association tests analyzed relationships between variables of interest at diagnosis. Two hundred fifty-five patients were included. Median age at diagnosis was 12.5 y (range: 1.6-18 y); median duration of symptoms prior to diagnosis was 3 m (range: 1-12 m). Neonatal history and previous medical history did not influence disease onset nor disease behavior. Fifty three % of these patients presented with a BMI z-score < -1. CRP was an independent predictor of disease severity. Steroids were widely used as initial treatment in moderate to severe and extensive disease. Over time, immunomodulators and biological were prescribed more frequently, reflecting a lower prescription rate for steroids and 5-ASA. A positive family history was the sole significant determinant for earlier use of immunosuppression. In Belgium, the median age of children presenting with Crohn's disease is 12.5 y. Faltering growth, extensive disease and upper GI involvement are frequent. CRP is an independent predictive factor of disease activity. A positive family history appears to be the main determinant for initial treatment choice. Copyright © 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.
Prassopoulos, P; Papanikolaou, N; Grammatikakis, J; Rousomoustakaki, M; Maris, T; Gourtsoyiannis, N
Magnetic resonance (MR) enteroclysis imaging is emerging as a technique for evaluation of the small bowel in patients with Crohn disease. Administration of 1.5-2 L of isosmotic water solution through a nasojejunal catheter ensures distention of the bowel and facilitates identification of wall abnormalities. True fast imaging with steady-state precession (FISP), half-Fourier acquisition single-shot turbo spin-echo (HASTE), and postgadolinium T1-weighted three-dimensional fast low-angle shot sequences can be employed in a comprehensive and integrated MR enteroclysis examination protocol to overcome specific disadvantages of each of the sequences involved. Superficial abnormalities that are ideally delineated with conventional enteroclysis are not consistently depicted with MR enteroclysis. The characteristic transmural abnormalities of Crohn disease such as bowel wall thickening, linear ulcers, and cobblestoning are accurately shown with MR enteroclysis imaging, especially with the true FISP sequence. MR enteroclysis is comparable to conventional enteroclysis in the detection of the number and extent of involved small bowel segments and in the disclosure of luminal narrowing or prestenotic intestinal dilatation. The clinical utility of MR enteroclysis in Crohn disease has not been fully established. At present, the method may be used for follow-up studies of known disease, estimation of disease activity, and determination of the extramucosal extent and spread of the disease process.
Tarján, Z; Makó, E; Dévai, T; Tulassay, Z
Fifty-four patients with suspected Crohn's disease of the small bowel underwent ultrasound examination with graded compression. The pathologic sonographic findings were compared with the clinical, endoscopic and in 32 cases with the parallel performed CT and selective enterographic examinations. Of the 29 proven cases of Crohn's disease 26 (89.7%) had bowel wall thickening detectable with US. The change in the bowel wall structure correlated to the stage of the disease. The luminal narrowing, the mesenteric involvement, the enlargement of the mesenteric lymph nodes, the abscesses and fistulas were judged easily, but the length and the location of the bowel segment were estimated only approximately. The characteristic but nonspecific signs observed by ultrasound were found to be a useful adjunct to the endoscopic and roentgen examinations. The ultrasound with graded compression in our view is a well usable alternative method for both diagnosis and follow-up, informing about the transmural spread of the pathology.
Lewis, Robert T.; Bleier, Joshua I. S.
Crohn disease involves the perineum and rectum in approximately one-third of patients. Symptoms can range from mild, including skin tags and hemorrhoids, to unremitting and severe, requiring a proctectomy in a small, but significant, portion. Fistula-in-ano and perineal sepsis are the most frequent manifestation seen on presentation. Careful diagnosis, including magnetic resonance imaging or endorectal ultrasound with examination under anesthesia and aggressive medical management, usually with a tumor necrosis factor-alpha, is critical to success. Several options for definitive surgical repair are discussed, including fistulotomy, fibrin glue, anal fistula plug, endorectal advancement flap, and ligation of intersphincteric fistula tract procedure. All suffer from decreased efficacy in patients with Crohn disease. In the presence of active proctitis or perineal disease, no surgical therapy other than drainage of abscesses and loose seton placement is recommended, as iatrogenic injury and poor wound healing are common in that scenario. PMID:24436656
Summary Introduction The present review serves to provide a concise overview of the current knowledge on therapeutic strategies with regard to fibrostenotic lesions in Crohn's disease. Methods A literature search was performed focusing on the last 5 years, and current concepts of pathophysiology, epidemiology, and treatment have been summarized. Results Fibrostenotic lesions in Crohn's disease are currently considered to be a consequence of the chronic inflammatory nature of the disease. Hence, therapeutic strategies are limited to the concept that early treatment of the inflammatory lesions can prevent structural changes, and to various endoscopic and surgical approaches. Direct targeting of the fibrostenotic lesion itself has not been the focus until now. This review will provide an overview of the pathophysiology and epidemiology of fibrostenotic lesions including current therapeutic approaches. Since research with regard to other organ systems and fibrosis is far more advanced, current strategies from available studies in these areas will be discussed. The results and the potential impact for Crohn's disease will be considered. Conclusion The vision of these approaches is to reverse structural changes and restore normal function. PMID:26557834
The present review serves to provide a concise overview of the current knowledge on therapeutic strategies with regard to fibrostenotic lesions in Crohn's disease. A literature search was performed focusing on the last 5 years, and current concepts of pathophysiology, epidemiology, and treatment have been summarized. Fibrostenotic lesions in Crohn's disease are currently considered to be a consequence of the chronic inflammatory nature of the disease. Hence, therapeutic strategies are limited to the concept that early treatment of the inflammatory lesions can prevent structural changes, and to various endoscopic and surgical approaches. Direct targeting of the fibrostenotic lesion itself has not been the focus until now. This review will provide an overview of the pathophysiology and epidemiology of fibrostenotic lesions including current therapeutic approaches. Since research with regard to other organ systems and fibrosis is far more advanced, current strategies from available studies in these areas will be discussed. The results and the potential impact for Crohn's disease will be considered. The vision of these approaches is to reverse structural changes and restore normal function.
Furukawa, Akira; Saotome, Takao; Yamasaki, Michio; Maeda, Kiyosumi; Nitta, Norihisa; Takahashi, Masashi; Tsujikawa, Tomoyuki; Fujiyama, Yoshihide; Murata, Kiyoshi; Sakamoto, Tsutomu
The role of cross-sectional imaging in the diagnosis of Crohn disease has expanded with recent technologic advances in computed tomography (CT) and magnetic resonance (MR) imaging that allow rapid acquisition of high-resolution images of the intestines. To acquire images of diagnostic quality, administration of a fairly large amount of intraluminal contrast agent prior to examination and scanning with intravenous contrast material injection are necessary. Both CT and MR imaging are reported to have a sensitivity of over 95% for the detection of Crohn disease; however, they may not allow early diagnosis. Colonoscopy and conventional enteroclysis studies are indicated for patients with early-stage disease. At more advanced stages, CT and MR imaging can help identify and characterize pathologically altered bowel segments as well as extraluminal lesions (eg, fistulas, abscesses, fibrofatty proliferation, increased vascularity of the vasa recta, mesenteric lymphadenopathy). These modalities can also clearly depict inflammatory lesion activity and conditions that require elective gastrointestinal surgery, thereby aiding in treatment planning. In the clinical setting, CT is currently the imaging modality of choice at most institutions; however, it is expected that MR imaging will soon play a comparable role. CT or MR imaging should be included in a comprehensive evaluation of patients with Crohn disease, along with conventional imaging and clinical and laboratory tests.
Kiuru, Maija; Camp, Brendan; Adhami, Katayun; Jacob, Vinita; Magro, Cynthia; Wildman, Horatio
Metastatic Crohn disease is a rare cutaneous manifestation of Crohn disease characterized by granulomatous lesions discontinuous with the diseased areas of the gastrointestinal tract. We report a case of a 32-year-old woman with history of Crohn disease who was admitted for treatment of cellulitis after presenting with a tender erythematous plaque of the left calf. Microbiological tests including tissue cultures were negative. A skin biopsy revealed granulomatous dermatitis consistent with metastatic cutaneous Crohn disease. Owing to concomitant perianal fistulas and abscesses and prior infusion reaction to infliximab, the patient was treated with certolizumab, a pegylated tumor necrosis factor (TNF) inhibitor combined with methotrexate resulting in complete resolution of the skin lesion. This case emphasizes the importance of recognizing this rare skin manifestation of Crohn disease and adds certolizumab as one of TNF inhibitors useful in the treatment of metastatic cutaneous Crohn disease.
Hsu, Chien-Hui; Jeng, Yung-Ming; Ni, Yen-Hsuan
Crohn disease is a chronic inflammatory disorder, which is rare in pediatric patients. The definite etiology and mechanism to induce an acute exacerbation of Crohn disease remains mostly unknown. The authors report on a 14-year-old girl with Crohn disease who has acute gastrointestinal symptoms caused by toxin A-producing Clostridium difficile, which mimicked a flare-up of Crohn disease. There was no preceding antibiotic prescription before the episode. The disease activity did not improve after steroid treatment, which is unusual for Crohn disease. However, all symptoms were dramatically relieved after eradication of C difficile, and led to a symptom-free period for more than 3 years. This case report aims to address the unusual presentation of a usual pathogen, C difficile, in a pediatric patient with Crohn disease. Copyright © 2012. Published by Elsevier B.V.
Salva, Katrin A; Stenstrom, Melissa; Breadon, Jonith Y; Odland, Paul Blair; Bennett, Daniel; Longley, Jack; Wood, Gary S
IMPORTANCE Cutaneous Rosai-Dorfman disease (CRDD), a variant of Rosai-Dorfman disease limited to the skin, has a wide range of clinical presentations. Rosai-Dorfman disease is believed to result from an aberrant response to antigens, caused by immunosuppressive macrophages. Macrophage-mediated immunosuppression is also implicated in the pathogenesis of Crohn disease, linking these otherwise unrelated entities. To our knowledge, the coexistence of these disorders has been described in only 2 cases, 1 of them confined to the skin and soft tissue. OBSERVATIONS We present a series of 3 patients who developed purely CRDD in the context of long-standing Crohn disease. Statistical estimates suggested that the association of these 2 disorders is not due to chance (P<.001). CONCLUSIONS AND RELEVANCE Our case series provides the clinical correlate to the pathogenetic parallels between CRDD and Crohn disease. Crohn disease is frequently complicated by various skin manifestations, which may be mimicked by CRDD. Therefore, it may be prudent for clinicians to include CRDD in the list of differential diagnoses when examining skin lesions in patients with Crohn disease.
Salva, Katrin A.; Stenstrom, Melissa; Breadon, Jonith Y.; Odland, Paul Blair; Bennett, Daniel; Longley, Jack; Wood, Gary S.
IMPORTANCE Cutaneous Rosai-Dorfman disease (CRDD), a variant of Rosai-Dorfman disease limited to the skin, has a wide range of clinical presentations. Rosai-Dorfman disease is believed to result from an aberrant response to antigens, caused by immunosuppressive macrophages. Macrophage-mediated immunosuppression is also implicated in the pathogenesis of Crohn disease, linking these otherwise unrelated entities. To our knowledge, the coexistence of these disorders has been described in only 2 cases, 1 of them confined to the skin and soft tissue. OBSERVATIONS We present a series of 3 patients who developed purely CRDD in the context of long-standing Crohn disease. Statistical estimates suggested that the association of these 2 disorders is not due to chance (P < .001). CONCLUSIONS AND RELEVANCE Our case series provides the clinical correlate to the pathogenetic parallels between CRDD and Crohn disease. Crohn disease is frequently complicated by various skin manifestations, which may be mimicked by CRDD. Therefore, it may be prudent for clinicians to include CRDD in the list of differential diagnoses when examining skin lesions in patients with Crohn disease. PMID:24305684
Gecse, Krisztina; Khanna, Reena; Stoker, Jaap; Jenkins, John T; Gabe, Simon; Hahnloser, Dieter; D'Haens, Geert
Fistulizing Crohn's disease represents an evolving, yet unresolved, issue for multidisciplinary management. Perianal fistulas are the most frequent findings in fistulizing Crohn's disease. While enterocutaneous fistulas are rare, they are associated with considerable morbidity and mortality. Detailed evaluation of the fistula tract by advanced imaging techniques is required to determine the most suitable management options. The fundamentals of perianal fistula management are to evaluate the complexity of the fistula tract, and exclude proctitis and associated abscess. The main goals of the treatment are abscess drainage, which is mandatory, before initiating immunosuppressive medical therapy, resolution of fistula discharge, preservation of continence and, in the long term, avoidance of proctectomy with permanent stoma. The management of enterocutaneous fistulas comprises of sepsis control, skin care, nutritional optimization and, if needed, delayed surgery.
Boers-Sonderen, Marye J; Mulder, Sasja F; Nagtegaal, Iris D; Jacobs, Joannes F M; Wanten, Geert J; Hoentjen, Frank; van Herpen, Carla M
Sunitinib is a multiple tyrosine kinase inhibitor of the vascular endothelial growth factor and platelet-derived growth factor pathway and inhibits angiogenesis, cell proliferation, and tumor cell invasion, and stimulates apoptosis. Treatment with sunitinib in first-line metastatic renal cell carcinoma improves progression-free survival and overall survival compared with interferon-α. Crohn's disease is characterized by chronic immune-mediated intestinal inflammation. Although the exact pathogenesis of Crohn's disease remains unknown, the involvement of angiogenesis is acknowledged. It is unknown whether sunitinib interferes with the natural course of Crohn's disease. We describe a patient with metastatic renal cell carcinoma and a history of Crohn's disease who was treated with sunitinib and developed a severe exacerbation of Crohn's disease. After rechallenge with sunitinib, a second exacerbation occurred. We therefore conclude that angiogenesis inhibitors should be administered with care in patients with a history of Crohn's disease.
Lakatos, László; Lakatos, Péter László
The therapy of inflammatory bowel diseases is based on 5-aminosalicylates (5-ASAs) that are the forefront of treatment of mild-to-moderate active disease and maintenance; steroids are used for the treatment of moderate-to-severe active disease; immunosuppressives and sometimes antibiotics in moderate-to-severe disease; maintenance and for the treatment of selected complications. The last few years have witnessed a significant change in the treatment of Crohn's disease. Based on evidence from new clinical studies and recent meta-analyses, the role of and indications for conventional therapy have been reassessed. The 5-ASAs are nowadays less frequently used in both active disease and maintenance therapy. Instead, budesonide has been introduced in the treatment of mild-to-moderate ileal disease. Besides the modest use of 5-ASAs, steroids are prescribed for active colonic disease. Immunosuppressives, especially azathioprine, are more commonly used in moderate-to-severe disease as well as in maintenance. The preferred maintenance regimen following medically- and surgically-induced remission, in addition to relationship between medical and surgical therapies, has also changed. The recent introduction of new "biological" therapy represents a major, promising change in the therapy of resistant and penetrating disease.
Sinha, Rakesh; Rajiah, Prabhakar; Murphy, Paul; Hawker, Peter; Sanders, Scott
Magnetic resonance (MR) imaging has emerged as an imaging modality that can be used to help diagnose and evaluate Crohn disease of the small and large bowel. MR imaging has high diagnostic accuracy in the detection of Crohn disease, and high-resolution thin-section MR images can demonstrate transmural pathologic changes of Crohn disease from the level of the mucosa to that of the mesentery. High-resolution MR image data also may be used to construct high-quality multiplanar and endoluminal views that may provide additional diagnostic information. Knowledge of the MR imaging findings of Crohn disease and how they correlate with the pathologic features of the disease is important to facilitate accurate diagnosis and detect complications.
Leyendecker, John R; Bloomfeld, Richard S; DiSantis, David J; Waters, Gregory S; Mott, Ryan; Bechtold, Robert E
Crohn disease is a complex pathologic process with an unpredictable lifelong course that includes frequent relapses. It often affects young patients, who are most vulnerable to the potential adverse effects of repeated exposure to ionizing radiation from computed tomography performed for diagnosis and surgical planning. The small intestine is the bowel segment that is most frequently affected, but it is the least accessible with endoscopic techniques. Magnetic resonance (MR) enterography has the potential to safely and noninvasively meet the imaging needs of patients with Crohn disease without exposing them to ionizing radiation. Appropriate use of MR enterography requires a carefully crafted protocol to depict signs of active inflammation as well as complications such as bowel obstruction, fistulas, and abscesses. Interpretation of MR enterographic images requires familiarity with the imaging signs and mimics of active bowel inflammation and stenosis. Although MR enterography currently is helpful for management in individual patients, the standardization of acquisition protocols and interpretive methods would increase its usefulness for more rigorous, systematic assessments of Crohn disease treatment regimens.
... Conditions Crohn's disease Is fatigue a common Crohn's disease symptom? What can be done about it? Answers from ... M.D. Fatigue is an all too common symptom of Crohn's disease. In one study, about three-quarters of people ...
Linaker, B. D.
A case of scurvy presenting in a patient with Crohn's disease is reported. A normal response to replacement therapy is seen. Vitamin C (ascorbic acid) deficiency was found in 7 out of 10 patients with clinically quiescent Crohn's disease, 4 of whom had an adequate oral intake of vitamin C. There was no significant difference in oral intake between patients with Crohn's disease and matched controls but there was a significant difference (P less than 0.001) in leucocyte ascorbic acid levels. It is recommended that patients with Crohn's disease be screened for vitamin C deficiency and receive prophylactic vitamin C supplements daily. PMID:432168
Chen, Merry; Lee, Grace; Kwong, Lawrence N; Lamont, Sharon; Chaves, Claudia
To investigate the incidence, characteristics, and predisposing factors for cerebral white matter lesions in patients with Crohn's disease. We retrospectively evaluated the incidence and characteristics of cerebral T2 white matter abnormalities in 54 patients with Crohn's disease and compared to 100 age-matched controls. We also investigated potential co-morbidities known to be associated with white matter abnormalities in Crohn's patients with normal and abnormal Magnetic Resonance Imaging (MRI). Seventy-two percent of patients with Crohn's disease had T2 white matter abnormalities, as compared with 34% of the age-matched controls (P < .001). Lesion severity and size were not significantly different between the two groups; however, periventricular distribution and fulfillment of the Barkhof MRI criteria were overrepresented in Crohn's population. History of hypertension, diabetes, and migraine; gender, duration of disease and prior exposure to anti-tumor necrosis factor were not significantly different between Crohn's patients with and without white matter abnormalities; however, patients with lesions were significantly older than those without. Patients with Crohn's disease have a higher incidence of white matter T2 hyperintensities as compared with controls. Age was the only significant factor for the abnormalities within Crohn's group. White matter T2 hyperintensities are likely another extra-intestinal manifestation of Crohn's disease. Copyright © 2010 by the American Society of Neuroimaging.
Lazzerini, Marzia; Martelossi, Stefano; Cont, Gabriele; Bersanini, Chiara; Ventura, Giovanna; Fontana, Massimo; Zuin, Giovanna; Ventura, Alessandro; Taddio, Andrea
The term orofacial granulomatosis is conventionally used to describe patients with granulomatous lesions affecting the orofacial tissues, in absence of intestinal lesions. Lip swelling and facial swelling are the most common clinical signs. Despite the fact that histologically it is not distinguishable from Crohn's disease, and that both diseases have a chronic/recurrent course, the relationship between orofacial granulomatosis and Crohn's disease is still debated. Herein we present five cases of orofacial granulomatosis. All patients presented concomitant Crohn's disease, supporting the hypothesis that orofacial granulomatosis and Crohn's disease may be one single disease. Thalidomide was effective in inducing remission of oral and intestinal symptoms in all five cases and could be considered a valid treatment opportunity for these patients. Orofacial granulomatosis and Crohn's disease may be part of the same disease; both may respond to thalidomide. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
Szurowska, Edyta; Wypych, Joanna; Izycka-Swieszewska, Ewa
Crohn's disease is a chronic, transmural inflammatory process of the gastrointestinal tract. It often affects the colon with the perianal area. The most common intestinal manifestations include external and/or internal fistulas and abscesses. Assessment of the activity of perianal fistulas in the course of Crohn's disease seems to be an important factor influencing therapeutic approach. Fistula's activity is evaluated by such methods as magnetic resonance imaging, anal ultrasound and examination under anaesthesia. Usefulness of imaging methods in the diagnosis of fistulas still remains to be defined.MRI is used to present a wide spectrum of perianal fistulazing Crohn's disease. Additionally, it is an important instrument revealing location, extent and severity of inflammation. It is also very helpful to detect clinically silent sepsis related to small, local inflammation. The most common method used in MR imaging to assess topography of a fistula's track, is Parks' classification.Clinical indications to MRI may include follow-up studies of a diagnosed disease, classification of fistulas' subtypes in the course of Crohn's disease, determination of the extent of fistulas' tracts and spread of an inflammatory process what can guide surgical procedures.
Kündiger, T; Wirths, K; Wegjan, E; Zöpf, T
We report on a 48-year-old patient with Crohn's disease and left abdominal pain, who presented with hematuria and proteinuria. As reason we found a left renal vein thrombosis. This diagnosis was based on magnetic resonance imaging and doppler ultrasound. The incidence of thrombembolic complications in patients with chronic inflammatory bowel disease is increased, however renal vein thrombosis is a very rare complication of Crohn's disease. We started a conservative treatment with phenprocoumon. Thereafter the patient remained asymptomatic and the thrombus dissipated during follow-up.
McNees, Adrienne L; Markesich, Diane; Zayyani, Najah R; Graham, David Y
Crohn's disease is a chronic inflammatory bowel disease of unknown cause, affecting approximately 1.4 million North American people. Due to the similarities between Crohn's disease and Johne's disease, a chronic enteritis in ruminant animals caused by Mycobacterium avium paratuberculosis (MAP) infection, MAP has long been considered to be a potential cause of Crohn's disease. MAP is an obligate intracellular pathogen that cannot replicate outside of animal hosts. MAP is widespread in dairy cattle and because of environmental contamination and resistance to pasteurization and chlorination, humans are frequently exposed through contamination of food and water. MAP can be cultured from the peripheral mononuclear cells from 50-100% of patients with Crohn's disease, and less frequently from healthy individuals. Association does not prove causation. We discuss the current data regarding MAP as a potential cause of Crohn's disease and outline what data will be required to firmly prove or disprove the hypothesis.
McNees, Adrienne L.; Markesich, Diane; Zayyani, Najah R.; Graham, David Y.
SUMMARY Crohn's disease is a chronic inflammatory bowel disease of unknown cause, affecting approximately 1.4 million North American people. Due to the similarities between Crohn's disease and Johne’s disease, a chronic enteritis in ruminant animals caused by Mycobacterium avium paratuberculosis (MAP) infection, MAP has long been considered to be a potential cause of Crohn's disease. MAP is an obligate intracellular pathogen that cannot replicate outside of animal hosts. MAP is widespread in dairy cattle and because of environmental contamination and resistance to pasteurization and chlorination, humans are frequently exposed through contamination of food and water. MAP can be cultured from the peripheral mononuclear cells from 50 to 100% of patients with Crohn's disease, and less frequently from healthy individuals. Association does not prove causation. We discuss the current data regarding MAP as a potential cause of Crohn's disease and outline what data will be required to firmly prove or disprove the hypothesis. PMID:26474349
Su, Yann-Rong; Shih, I-Lun; Tai, Huai-Ching; Wei, Shu-Chen; Lin, Been-Ren; Yu, Hong-Jeng; Huang, Chao-Yuan
Crohn disease is a chronic, transmural, inflammatory disease of the gastrointestinal tract with unknown etiology. It can affect any part of the gastrointestinal tract and may cause fistula, stricture, or abscess formation with disease progression. The preoperative diagnosis and definite management of this rare complication are challenges for physicians, urologists, and surgeons. PMID:24670020
... an affected family member is a significant risk factor for the disease. Related ... Bernard EJ, Mei L, Nicolae DL, Regueiro M, Schumm LP, Steinhart AH, Rotter JI, Duerr RH, Cho JH, Daly MJ, Brant SR. Genome-wide ...
Braithwaite, Kiery A; Alazraki, Adina L
Development of internal fistula due to extramural spread of inflammatory bowel disease is a characteristic feature of penetrating disease in patients with Crohn disease. The "star sign" is a radiological finding of internal fistula that has previously been described in the gastroenterology literature in adult Crohn disease patients undergoing MR enteroclysis. The goal of this paper is to review the clinical and imaging features of penetrating disease in pediatric Crohn disease patients, highlighting the star sign as a useful diagnostic tool for diagnosing internal fistula in children by MR enterography. The recognition of penetrating complications by MR imaging can have important therapeutic and prognostic implications.
Tsai, Timothy L; Marine, Megan B; Wanner, Matthew R; Cooper, Matthew L; Steiner, Steven J; Ouyang, Fangqian; Gregory Jennings, S; Karmazyn, Boaz
There is growing literature on the use of ultrasound (US) for evaluation of Crohn disease in adults, but few studies have been conducted on children. Several studies demonstrated high accuracy of US in the diagnosis of Crohn disease. Using US as the primary screening imaging modality for Crohn disease can reduce health care costs, the need for sedation and ionizing radiation exposure. The aim of our study is to determine if US can be used for screening evaluation of pediatric Crohn disease. A prospective cohort study of pediatric patients undergoing MR enterography (MRE) for suspected or known history of Crohn disease was performed, with gray-scale and Doppler US of the terminal ileum done immediately before or after MRE. US images were interpreted by two radiologists (Reader 1 and Reader 2) not involved in image acquisition, in blinded and randomized fashion. US findings of Crohn disease including bowel wall thickening, wall stratification, increased vascularity on Doppler, lymphadenopathy, fat infiltration and extraintestinal complications were evaluated. MRE findings of terminal ileitis were considered the reference standard. Demographic data, body mass index (BMI), symptoms, and laboratory, endoscopic and histopathological data were obtained from electronic medical records. Forty-one patients (mean age: 13.7 years: 4.6-18.9 years) were evaluated. Mean BMI was 21.2 (range: 13-40.2); 10 patients (24.3%) were either overweight or obese. Final diagnoses were Crohn disease (n=24), ulcerative colitis (n=4) and normal/non-inflammatory bowel disease-related diagnoses (n=13). US demonstrated sensitivity of 67% and 78% and specificity of 78% and 83%, by Reader 1 and Reader 2, respectively. MRE sensitivity and specificity were 75% and 100%, respectively, compared to final clinicopathological diagnosis. Interobserver agreement between Reader 1 and Reader 2 was good (0.6< kappa <0.8). In screening for Crohn disease in children, US has limited sensitivity for detecting
Le Luyer, B; Morin, C L; Roy, C C; Weber, A; Chouraqui, J P; Bensoussan, A
93 children and adolescents with Crohn's disease have been studied. Terminal ileum (25.8%) and ileum and colon (61.3%) were the most common sites of involvement as determined by X-ray examination. The mean age at the time of diagnosis was 13.2 years. A familial incidence of chronic inflammatory bowel disease was found in 12 patients (12.9%). The most common symptoms were: abdominal pain, anorexia, lassitude, diarrhea, loss of weight. Weight below the third percentile, pain on abdominal palpation, anal lesions, mouth ulcers and clubbing of the fingers were the most common clinical signs at the time of diagnosis. Growth retardation (below the third percentile) was present in 22 of 79 children (27.8%) with a mean follow-up of 40 months. 16 patients out of 75 had initial rectal biopsies with histologic changes characteristic of Crohn's disease. 27 patients had surgical treatment; six of them experienced a relapse within a mean period of 26.7 months. Lastly, the authors show that continuous elemental enteral alimentation (CEEA) during 3 weeks induces a remission. CEEA on a longer period is specially targetted to the treatment of growth retardation.
Yanagida, Hidehiko; Sugimoto, Keisuke; Izu, Akane; Wada, Norihisa; Sakata, Naoki; Takemura, Tsukasa
Development of both Crohn disease and Guillain-Barré syndrome likely involves autoimmunity associated with excessive inflammatory cytokines. We treated a girl who developed Guillain-Barré syndrome during the course of Crohn disease. Although high-dose γ-globulin therapy administered initially for Guillain-Barré syndrome was ineffective, plasmapheresis ameliorated her acute neuropathic symptoms. Crohn disease was managed with Salazopyrin administration and enteral feeding. Chronic inflammation of the intestinal mucosa caused by Crohn disease can allow presentation of microbial intestinal antigens normally hidden from the immune system. Such presentation could incite an extraintestinal immune response on the basis of molecular mimicry, leading to activation of systemic autoimmunity against the nervous system. Accordingly, concurrence of Guillain-Barré syndrome and Crohn disease in our patient appeared to result from shared autoimmune mechanisms and systemic and local increases in cytokine concentrations. The patient also developed erythema nodosum and gall stones, relatively common complications of Crohn disease. However, Guillain-Barré syndrome is rare.
Jansson, J.K.; Willing, B.; Lucio, M.; Fekete, A.; Dicksved, J.; Halfvarson, J.; Tysk, C.; Schmitt-Kopplin, P.
The causes and etiology of Crohn's disease (CD) are currently unknown although both host genetics and environmental factors play a role. Here we used non-targeted metabolic profiling to determine the contribution of metabolites produced by the gut microbiota towards disease status of the host. Ion Cyclotron Resonance Fourier Transform Mass Spectrometry (ICR-FT/MS) was used to discern the masses of thousands of metabolites in fecal samples collected from 17 identical twin pairs, including healthy individuals and those with CD. Pathways with differentiating metabolites included those involved in the metabolism and or synthesis of amino acids, fatty acids, bile acids and arachidonic acid. Several metabolites were positively or negatively correlated to the disease phenotype and to specific microbes previously characterized in the same samples. Our data reveal novel differentiating metabolites for CD that may provide diagnostic biomarkers and/or monitoring tools as well as insight into potential targets for disease therapy and prevention.
Hefaiedh, Rania; Sabbeh, Mariem; Miloudi, Nizar; Ennaifer, Rym; Romdhane, Hayfa; Belhadj, Najet; Gharbi, Lassad; Khalfallah, Tahar
Crohn's disease management represents a major problem in gastroenterology and general surgery because it affects young subjects and has a major impact on their quality of life. The aims of our study were to identify the indications for surgery in Crohn's disease, the results and the complications of surgery in our series, and to identify possible predictive factors of recurrence and postoperative morbidity. A retrospective descriptive study including 38 cases of patients with Crohn's disease who underwent surgical treatment in the department of surgery in Mongi Slim Hospital, during the period between January 1992 and December 2011 was performed. The occurrence of stenosis was the most common indication for surgical treatment in Crohn's disease in our series, and ileocecal resection was the most performed surgery. Twenty six patients (58%) received maintenance therapy after surgery. Twenty two patients relapsed and 13 had surgical management for recurrence. In univariate analysis, predictive factors of post operative morbidity in our study were leukocytosis, penetrating phenotype and intraabdominal sepsis. Ileocecal location was the only factor that significantly improved the incidence of recurrence. In multivariate analysis, only penetrating phenotype was a predictive factor or post operative morbidity. Despite the development of medical treatment, surgical treatment keeps large indications for the management of complications of Crohn's disease. The surgery should be an alternative to immunosuppressive therapy. Currently, prevention postoperative recurrence is well codified, reducing the risk of complications.
Lakatos, László; Lakatos, Péter László
Crohn's disease is a chronic, progressive disabling condition ultimately leading to stricturing and/or penetrating complications. The need for surgery may be as high as 70% in patients with severe active disease or complications. However, relapse may develop in a significant proportion of the patients after surgery leading to frequent re-operations. Despite emerging data, postoperative prevention is still controversial. After careful evaluation of the individual risk a tailored therapy should be considered. In patients with small risk for relapse mesalazine or in selected cases no-treatment may be an option. In patients with a moderate-to-high risk azathioprine should be considered together with metronidazole in the three months. Follow-up ileocolonoscopy 6-12 months after the surgery is helpful in the determination of endoscopic severity and may assist in the optimization of the therapy. In most severe cases anti-TNF agents may be appropriate for postoperative prevention and therapy.
Butnor, Kelly J; Pavlisko, Elizabeth N; Sporn, Thomas A; Roggli, Victor L
Mesothelial reaction simulating peritoneal diffuse malignant mesothelioma (MM) has been reported in the setting of Crohn ileitis. To our knowledge, peritoneal MM arising in patients with inflammatory bowel disease (IBD) has not been reported. The purpose of this study is to report the clinicopathological characteristics of patients with peritoneal MM and IBD. A database of approximately 3800 MM was reviewed for cases of MM in patients with IBD. Three patients (0.08%) with peritoneal MM and Crohn disease (CD) were identified, including two women and one man ranging in age from 56 to 65 years. All had a long-standing history of diarrhoea and an established diagnosis of CD of 3 years or greater duration. Two had epithelial MM and one had biphasic MM. Only one had documented asbestos exposure. Peritoneal MM occurs rarely in patients with IBD, but interestingly, has only been observed in the setting of CD and not in patients with ulcerative colitis. Chronic inflammation has been associated with the development of MM in rare instances and these three cases suggest that CD with transmural inflammation may also be a precursor. The precise role of CD-related transmural inflammation in the carcinogenesis of peritoneal MM remains to be determined. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Kakkar, Aarti; Wasan, Sharmeel K.
The goal of medical treatment for Crohn's disease includes improving patients' quality of life while reducing the need for hospitalization and surgery. The current medical armamentarium includes 5-aminosalicylates, corticosteroids, immunomodulators, and biologic agents. In the past, response to treatment was measured by clinical improvement in symptoms; however, with the advent of disease-modifying medications, mucosal healing has emerged as an increasingly important goal of therapy. Mucosal healing, or endoscopic remission, is associated with increased rates of clinical remission, fewer hospitalizations, and fewer abdominal surgeries. Both the immunomodulator and biologic classes of medications are effective at inducing mucosal healing. Despite several limitations, mucosal healing has become a desirable and valid measure of disease activity. PMID:21869869
Stappenbeck, Thaddeus S; Rioux, John D; Mizoguchi, Atsushi; Saitoh, Tatsuya; Huett, Alan; Darfeuille-Michaud, Arlette; Wileman, Tom; Mizushima, Noboru; Carding, Simon; Akira, Shizuo; Parkes, Miles; Xavier, Ramnik J
Crohn disease (CD) is a chronic and debilitating inflammatory condition of the gastrointestinal tract. Prevalence in Western populations is 100-150/100,000 and somewhat higher in Ashkenazi Jews. Peak incidence is in early adult life, although any age can be affected and a majority of affected individuals progress to relapsing and chronic disease. Medical treatments rely significantly on empirical corticosteroid therapy and immunosuppression, and intestinal resectional surgery is frequently required. Thus, 80% of patients with CD come to surgery for refractory disease or complications. It is hoped that an improved understanding of pathogenic mechanisms, for example by studying the genetic basis of CD and other forms of inflammatory bowel diseases (IBD), will lead to improved therapies and possibly preventative strategies in individuals identified as being at risk.
Michelassi, Fabrizio; Sultan, Samuel
The clinical presentations of Crohn disease of the small bowel vary from low to high complexity. Understanding the complexity of Crohn disease of the small bowel is important for the surgeon and the gastroenterologist caring for the patient and may be relevant for clinical research as a way to compare outcomes. Here, we present a categorization of complex small bowel Crohn disease and review its surgical treatment as a potential initial step toward the establishment of a definition of complex disease. The complexity of small bowel Crohn disease can be sorted into several categories: technical challenges, namely, fistulae, abscesses, bowel or ureteral obstruction, hemorrhage, cancer and thickened mesentery; extensive disease; the presence of short gut; a history of prolonged use of medications, particularly steroids, immunomodulators, and biological agents; and a high risk of recurrence. Although the principles of modern surgical treatment of Crohn disease have evolved to bowel conservation such as strictureplasty techniques and limited resection margins, such practices by themselves are often not sufficient for the management of complex small bowel Crohn disease. This manuscript reviews each category of complex small bowel Crohn disease, with special emphasis on appropriate surgical strategy.
Warwick, G; Leecy, T; Silverstone, E; Rainer, S; Feller, R; Yates, D H
The present article reports the case of a 22-yr-old female with new onset Crohn's colitis, anterior uveitis and multiple pulmonary nodules which, on histological examination, were necrobiotic nodules. This is a rare but recognised pulmonary extraintestinal manifestation of Crohn's disease and only the fourth reported case. The present case report is followed by a brief review of the relevant literature.
Yamamoto, Takayuki; Shimoyama, Takahiro; Kuriyama, Moeko
It is now widely acknowledged that the intestinal bacterial flora together with genetic predisposing factors significantly contribute to the immunopathogenesis of inflammatory bowel disease (IBD) as reflected by mucosal immune dysregulation. Recently, there has been an increased interest in nutraceutical therapies, including probiotics, prebiotics and synbiotics. Other dietary interventions with low carbohydrate diet, omega-3 polyunsaturated fatty acids and glutamine have been attempted to downregulate the gut inflammatory response and thereby alleviate gastrointestinal symptoms. Enteral nutrition has been widely used as induction and maintenance therapies in the management of Crohn's disease (CD). In this review, a critical assessment of the results of clinical trial outcomes and meta-analyses was conducted to evaluate the efficacy of dietary and enteral interventions for CD.
Sordo-Mejia, Ricardo; Gaertner, Wolfgang B
Perianal symptoms are common in patients with Crohn's disease and cause considerable morbidity. The etiology of these symptoms include skin tags, ulcers, fissures, abscesses, fistulas or stenoses. Fistula is the most common perianal manifestation. Multiple treatment options exist although very few are evidence-based. The phases of treatment include: drainage of infection, assessment of Crohn's disease status and fistula tracts, medical therapy, and selective operative management. The impact of biological therapy on perianal Crohn's disease is uncertain given that outcomes are conflicting. Operative treatment to eradicate the fistula tract can be attempted once infection has resolved and Crohn's disease activity is controlled. The operative approach should be tailored according to the anatomy of the fistula tract. Definitive treatment is challenging with medical and operative treatment rarely leading to true healing with frequent complications and recurrence. Treatment success must be weighed against the risk of complications, specially anal sphincter injury. A full understanding of the etiology and all potential therapeutic options is critical for success. Multidisciplinary management of fistulizing perianal Crohn's disease is crucial to improve outcomes.
García Martínez, F J; Menchén, L
Both hidradenitis suppurativa and Crohn disease are considered chronic inflammatory diseases due to immune dysregulation. The high prevalence of Crohn disease patients diagnosed with hidradenitis suppurativa suggests the existence of common pathogenic links. The present literature review analyses the similarities and differences in the pathogenesis of the two diseases, in the search for new research and knowledge targets. Copyright © 2016 Elsevier España, S.L.U. y AEDV. All rights reserved.
Konno, Mutsuko; Kobayashi, Akio; Tomomasa, Takeshi; Kaneko, Hiroaki; Toyoda, Shigeru; Nakazato, Yutaka; Nezu, Riichiro; Maisawa, Shun-Ichi; Miki, Kazunori
This paper shows guidelines for the treatment of Crohn's disease in children by the Working Group of the Japanese Society for Pediatric Gastroenterology, Hepatology and Nutrition (Chair: Yuichiro Yamashiro) and the Japanese Society for Pediatric Inflammatory Bowel Disease (Chair: Akio Kobayashi). The points in which these guidelines differ from those for adult patients are as follows. (i) Total enteral nutrition in the form of an elemental formula is indicated as primary therapy for children with Crohn's disease at onset as well as the active stage. Oral mesalazine is used together. (ii) Total parenteral nutrition (TPN) with oral mesalazine is required for children with serious illness. The use of a corticosteroid should be withheld for at least 1 week after TPN has been started. (iii) When TPN is not considered to be effective, additional corticosteroid is used. Full doses of corticosteroid should be used for at least 2 weeks after clinical improvement has been achieved, and then the dose of the corticosteroid should be tapered carefully. (iv) When surgery is indicated in pediatric patients with stricture or fistula formation and complicated by persistent growth failure despite medical therapy, the optimum time for surgery is thought to be before epiphyseal plates have been closed.
Hashash, Jana G; Regueiro, Miguel
Postoperative Crohn's disease recurrence remains common, and preventing additional surgery remains a challenge. A critical step to postoperative management of Crohn's disease is being able to identify patients who should receive immediate postoperative therapy from the patients who can wait for recurrence prior to starting medications. All patients, regardless of their risk for recurrence, are advised to undergo a colonoscopy at 6 to 12 months after surgery to evaluate for endoscopic evidence of Crohn's disease. Further management of patients depends on symptoms and the presence or absence of endoscopic recurrence.
Hill, Rj; Lewindon, Pj; Muir, R; Grangé, I; Connor, Fl; Ee, Lc; Withers, Gd; Cleghorn, Gj; Davies, Psw
: Quality of life (QOL) is reportedly poor in children with Crohn disease (CD) but improves with increasing disease duration. This article aims to detail QOL in a cohort of Australian children with CD in relation to disease duration, disease activity, and treatment. : QOL, assessed using the IMPACT-III questionnaire, and disease activity measures, assessed using the Pediatric Crohn's Disease Activity Index (PCDAI), were available in 41 children with CD. For this cohort, a total of 186 measurements of both parameters were available. : QOL was found to be significantly lower, and disease activity significantly higher (F = 31.1, P = 0.00), in patients within 6 months of their diagnosis compared with those up to 2.5 years, up to 5 years, and beyond 5 years since diagnosis. Higher disease activity was associated with poorer QOL (r = -0.51, P = 0.00). Total QOL was highest in children on nil medications and lowest in children on enteral nutrition. The PCDAI (t = -6.0, P = 0.00) was a significant predictor of QOL, with the clinical history (t = -6.9, P = 0.00) and examination (t = -2.9, P = 0.01) sections of the PCDAI significantly predicting QOL. Disease duration, age, or sex was neither related to nor significant predictors of QOL, but height z score and type of treatment approached significance. : Children with CD within 6 months of their diagnosis have impaired QOL compared with those diagnosed beyond 6 months. These patients, along with those with growth impairment, ongoing elevated disease activity with abdominal pain, diarrhoea and/or perirectal and extraintestinal complications, may benefit from regular assessments of QOL as part of their clinical treatment.
Alzoghaibi, Mohammed A
Oxygen free radical and lipid peroxides (oxidative stress) are highly reactive and represent very damaging compounds. Oxidative stress could be a major contributing factor to the tissue injury and fibrosis that characterize Crohn's disease. An imbalance between increased reactive oxygen species levels and decreased antioxidant defenses occurs in Crohn's patients. Decreased blood levels of vitamins C and E and decreased intestinal mucosal levels of CuZn superoxide dismutase, glutathione, vitamin A, C, E, and β-carotene have been reported for Crohn's patients. Increased levels of proinflammatory cytokines, such as interleukin-1 and -8 and tumor necrosis factor, have been detected in inflammatory bowel disease. Oxidative stress significantly increased the production of neutrophils, chemokines, and interleukin-8. These effects were inhibited by antioxidant vitamins and arachidonic acid metabolite inhibitors in human intestinal smooth muscle cells isolated from the bowels of Crohn's disease patients. The main pathological feature of Crohn's disease is an infiltration of polymorphonuclear neutrophils and mononuclear cells into the affected part of the intestine. Activated neutrophils produce noxious substances that cause inflammation and tissue injury. Due to the physiological and biochemical actions of reactive oxygen species and lipid peroxides, many of the clinical and pathophysiological features of Crohn's disease might be explained by an imbalance of increased reactive oxygen species and a net decrease of antioxidant molecules. This review describes the general concepts of free radical, lipid peroxide and antioxidant activities and eventually illustrates their interferences in the development of Crohn's strictures.
Ramos, Guilherme Piovezani; Faubion, William A; Papadakis, Konstantinos A
Understanding the immunologic pathways in intestinal inflammation is crucial for the development of new therapies that can maximize patient response and minimize toxicity. Targeting integrins and cytokines is intended to control leukocyte migration to effector sites or inhibit the action of proinflammatory cytokines. New approaches to preventing leukocyte migration may target integrin receptors expressed on the intestinal vascular endothelium. The interleukin (IL)-12/IL-23 pathway has been a therapeutic target of interest in controlling active Crohn's disease (CD). New therapeutic approaches in CD may involve the enhancement of anti-inflammatory cytokine pathways and modulation of cellular responses and intranuclear signals associated with intestinal inflammation. Copyright © 2017 Elsevier Inc. All rights reserved.
Øyri, Styrk Furnes; Műzes, Györgyi; Sipos, Ferenc
Since the first publication on "regional ileitis", the relevance of this chronic inflammatory disease condition termed finally as Crohn's disease is continuously increasing. Although we are beginning to comprehend certain aspects of its pathogenesis, many facets remain unexplored. Host's gut microbiota is involved in a wide range of physiological and pathological processes including immune system development, and pathogen regulation. Further, the microbiome is thought to play a key role in Crohn's disease. The presence of Crohn's-associated variants of NOD2 and ATG16L genes appears to be associated not only with alterations of mucosal barrier functions, and bacterial killing, but the gut microbiota, as well, reflecting a potential relationship between the host's genotype and intestinal dysbiosis, involved in disease etiology. This review aims to characterize some exciting new aspect of Crohn's disease pathology, focusing mainly on the role of intestinal microbes, and their interplay with the immune system of the host.
Hizawa, Kazuoki; Nagata, Yuko; Taniguchi, Masahiko; Nakamori, Mari; Matsumoto, Takayuki; Iida, Mitsuo
We describe a case of 36-year-old Japanese man with Crohn's disease, complicated by Bacillus cereus bacteremia on maintenance azathioprine therapy. Although anti-microbial agents were ineffective, the patient became well immediately after a partial resection of the ileum with multiple severe stenosis.
Rozpondek, Piotr; Zwolińska-Wcisło, Małgorzata; Przybylska, Magdalena; Mach, Tomasz
About 35% of patients with Crohn's disease develop fistulae. Treatment of those changes is a complicated clinical problem. Anti-TNF alpha antibodies are currently the most effective therapy of fistulizing Crohn's disease. Aim of the study is to evaluate results of anti-TNF alpha treatment in patients with fistulizing Crohn's disease. We evaluated results of anti-TNF alpha treatment (both with adalimumab n=10 and infliximab n=19) in 29 patients with fistulizing Crohn's disease treated in years 2008 - 2011 in Gastroenterology and Hepatology Clinic of University Hospital in Krakow. Closure of over 50% of fistulas was achieved by 78,94% patients after induction therapy with infliximab and 50% with adalimumab. Long term remission, evaluated after 52 weeks of treatment, was observed in 46,15% patients treated with infliximab. Best results were observed in perianal fistulas treatment - remission was achieved in 88.2% of patients. Effectiveness of enterocutaneus fistalas therapy was lower, and their healing was observed in 28.57% of patients. We observed no correlation between duration of Crohn's disease, duration of fistulas history or previously used treatment and results of anti-TNF alpha treatment. Anti-TNF alpha treatment has high effectiveness both short and long term in fistulizing Crohn's disease. Tolerance of treatment is very good. We lack clinical data about treatment other fistulas than perianal, but we suspect that effectiveness of anti-TNF alpha in this cases is lower. It is indicated to treat patients with fistulizing Crohn's disease with anti-TNF alpha, because it gives them chance for long remission and improvement of quality of life.
Hindryckx, Pieter; Baert, Filip; Hart, Ailsa; Armuzzi, Alessandro; Panès, Julian; Peyrin-Biroulet, Laurent
It goes back to 1932 when Dr. Burrill Bernard Crohn and co-workers published their landmark paper, describing regional ileitis as a disease entity. However, clinical trial research has been developing rather slowly in luminal Crohn's disease. It took until the early seventies before the first randomized clinical trial was set up by the National Co-operative Crohn's Disease Study (NCCDS) group. Although the efforts of this group triggered a first wave of clinical trials in Crohn's disease, the lack of guidelines for conducting a clinical trial in this research area resulted in a variety of study designs and much criticism. Besides having a rather small sample size and a short follow-up time, they were often characterized by vague and subjective assessment of disease activity and treatment response. Following the advent of a new and very potent drug class in the late nineties, the anti-TNF agents, investigators started to re-think their study protocols and the first guidelines were set up by the regulatory authorities. Over the last 15years, clinical trials in luminal Crohn's disease have been evolving significantly. Inclusion criteria have been shifting from clinical scores such as Crohn's Disease Activity Index (CDAI) to more objective disease activity parameters such as biomarkers (C-reactive protein and faecal calprotectin) and endoscopic lesions. Primary endpoints have been developing from clinical response to corticosteroid-free remission and more ambitious end-points such as mucosal healing. In this paper, we will give a historical overview on clinical trials in luminal Crohn's disease, before and within the biologic era, and provide insight into how they have shaped our current understanding of trial designs in Crohn's disease.
Rieder, F; Hamer, O; Gelbmann, C; Schölmerich, J; Gross, V; Feuerbach, S; Herfarth, H; Rogler, G
Esophageal involvement in Crohn's disease is very rare. In only a small subgroup of these patients -- up to date fourteen cases have been described in the literature -- the course of the illness may be complicated by esophageal fistula formation. The therapy for fistulizing esophageal Crohn's disease so far has been disappointing, recurrence and progression are likely, and surgery still is the primary treatment modality for refractory patients. We here present a case of severe Crohn's disease with an esophagobronchial fistula and the successful closure of the fistula tract with the novel liquid polymer sealant "Onyx". This approach offers a new option for the treatment of this rare complication of Crohn's disease and should be considered if surgery is not possible.
Schreiber, Stefan; Rosenstiel, Philip; Albrecht, Mario; Hampe, Jochen; Krawczak, Michael
Chronic inflammatory disorders such as Crohn disease, atopic eczema, asthma and psoriasis are triggered by hitherto unknown environmental factors that function on the background of some polygenic susceptibility. Recent technological advances have allowed us to unravel the genetic aetiology of these and other complex diseases. Using Crohn disease as an example, we show how the discovery of susceptibility genes furthers our understanding of the underlying disease mechanisms and how it will, ultimately, give rise to new therapeutic developments. The long-term goal of such endeavours is to develop targeted prophylactic strategies. These will probably target the molecular interaction on the mucosal surface between the products of the genome and the microbial metagenome of a patient.
... Crohn's disease, it can conserve portions of your GI tract and return you to the best possible ... of the digestive tract—also called the gastrointestinal (GI) tract. The part most commonly affected is the ...
Gonciarz, Maciej; Mularczyk, Aldona; Szkudłapski, Dawid; Piątek, Iwona; Kopała, Marek
Adalimumab is a subcutaneously administered recombinant fully human monoclonal antibody targeting tumor necrosis factor alpha. It has been approved for use in Poland to treat patients with Crohn's disease under the program of Polish National Health Found since 2010.
Bandzar, Sean; Gupta, Shabnam; Platt, Manu O
Crohn's disease is an autoimmune disorder that affects nearly 1.4 million Americans. The etiology of Crohn's disease is not completely understood, however, research has suggested a genetic link. There is currently no known cure for Crohn's disease and, as a result, most government-funded research is being conducted to increase the quality of life of afflicted patients (i.e. reducing chronic inflammation and alleviating growth impairment in pediatric patients). A number of treatment options are available including an alpha-4 integrin inhibitor and several TNF-alpha inhibitors. Furthermore, research is being conducted on several alternative treatment options to help understand exactly which cellular mechanisms (i.e. inducing apoptosis in leukocytes) are required for clinical efficacy. This review seeks to chronicle the current available treatment options for patients affected by Crohn's disease to aid in understanding potential cellular mechanistic requirements for an efficacious drug, and shed light on potential options for future treatment.
van Lent, Anja U; D'Haens, Geert R
The course of Crohn's disease (CD) is unpredictable and potentially destructive. The percentage of patients requiring surgery at some stage in their disease accumulates to over 70%. After resection of the affected intestine, reappearance of CD occurs in the majority of patients. Prophylactic medical therapy to reduce the rate of postoperative recurrence has been proven to be effective, yet the incidence of recurrence remains high. Patient profiling (risk stratification) is important in this postoperative setting. High-risk patients (associated with e.g. smoking, the need of repetitive surgery and penetrating disease) require strong immunosuppressive treatment, which should be commenced immediately after surgery, when recurrent disease activity begins. Additionally, early screening endoscopy should be performed to monitor treatment effect. The efficacy of thiopurines is shown to be higher than mesalazine or imidazole antibiotics alone for preventing and ameliorating endoscopic recurrence of CD postoperatively; however, anti-tumor necrosis factors (anti-TNFs) are increasingly considered the most potent agents. In patients with a risk factor for early postoperative recurrence, the first line of treatment is 6-mercaptopurine, in combination with imidazole antibiotics if tolerated, followed by anti-TNFs. When lesions are found at colonoscopy, therapy should be upscaled. We propose a treatment algorithm to direct therapeutic management of CD postoperatively. © 2013 S. Karger AG, Basel.
Domènech, Eugeni; López-Sanromán, Antonio; Nos, Pilar; Vera, Maribel; Chaparro, María; Esteve, María; Gisbert, Javier P; Mañosa, Míriam
Despite the availability of new, powerful drugs for Crohn's disease, a significant proportion of patients will undergo an intestinal resection to control the disease as it develops. In the absence of an effective preventative treatment, the appearance of new intestinal lesions after surgery for Crohn's disease is the norm; this is known as post-operative recurrence and may appear very early on, even a few weeks after the surgical resection. Furthermore, the drugs that are currently available for the prevention of post-operative recurrence have a limited effect; up to 50% of cases present recurrent Crohn's disease activity despite the preventative treatment, which may require further surgery with the consequent loss of intestinal function, leading some patients to suffer from short bowel syndrome as an irreversible complication. The management of Crohn's disease patients who undergo an intestinal resection should thus be geared towards prevention, early detection and, in the worst case scenario, the treatment of post-operative recurrence. This article reviews the natural history, diagnostic measures, monitoring, prevention and treatment of post-operative recurrence, and proposes recommendations based on existing knowledge. Copyright © 2017 Elsevier España, S.L.U., AEEH y AEG. All rights reserved.
Jethwa, H; Mann, S
We describe the case of a 45-year-old man with ankylosing spondylitis being treated with etanercept who presented with a 1 month history of abdominal pain. CT abdomen revealed an ileocaecal mass associated with an abscess, resulting in a laparotomy and right hemi-colectomy. Histology of the resected specimen showed the classical features of Crohn's disease. Etanercept was stopped and he was started on adalimumab. He is currently in clinical remission from both ankylosing spondylitis and Crohn's disease.
Aarons, Cary B
Crohn disease remains a challenging clinical entity, both medically and surgically. It frequently presents in early adulthood and imposes a lifetime exposure to chronic inflammation that can affect the entire gastrointestinal tract. Although the mainstay of therapy is treatment with immunomodulating drugs, ∼70 to 90% of patients with Crohn disease will ultimately require surgery. Furthermore, there are high rates of symptomatic recurrences that may also require surgical intervention over time. There is no definitive cure for Crohn disease and surgery is reserved for failed medical therapy or the complications of the disease, namely, obstruction, septic complications (abscess, perforation), and fistulas. However, the robust inflammatory environment during these periods is not always conducive to a minimally invasive surgical approach. Despite the inherent technical challenges, the literature has increasingly shown that laparoscopy for Crohn disease, in the appropriate setting, is feasible and safe. In fact, it offers many advantages, which are particularly beneficial to this subset of patients, such as fewer wound complications, a shortened hospital course, less tissue trauma and subsequent adhesion formation, and earlier resumption of oral intake and bowel function.
Marcuzzi, Annalisa; Bianco, Anna Monica; Girardelli, Martina; Tommasini, Alberto; Martelossi, Stefano; Monasta, Lorenzo; Crovella, Sergio
Crohn's disease is a complex disease in which genome, microbiome, and environment interact to produce the immunological background of the disease. Disease in childhood is more extensive and characterized by a rapid progression, leading to severe repercussions in the course of the disorder. Several genetic variations have been associated with an increased risk of developing the disease and most of these are also implicated in other autoimmune disorders. The gut has many tiers of defense against incursion by luminal microbes, including the epithelial barrier and the innate and adaptive immune responses. Moreover, recent evidence shows that bacterial and viral infections, as well as inflammasome genes and genes involved in the autophagy process, are implicated in Crohn's disease pathogenesis. The aim of this review is to establish how much the diagnostic system can improve, thus increasing the success of Crohn's disease diagnosis. The major expectation for the near future is to be able to anticipate the possible consequences of the disease already in childhood, thus preventing associated complications, and to choose the best treatment for each patient.
Bianco, Anna Monica; Girardelli, Martina; Tommasini, Alberto; Martelossi, Stefano
Crohn's disease is a complex disease in which genome, microbiome, and environment interact to produce the immunological background of the disease. Disease in childhood is more extensive and characterized by a rapid progression, leading to severe repercussions in the course of the disorder. Several genetic variations have been associated with an increased risk of developing the disease and most of these are also implicated in other autoimmune disorders. The gut has many tiers of defense against incursion by luminal microbes, including the epithelial barrier and the innate and adaptive immune responses. Moreover, recent evidence shows that bacterial and viral infections, as well as inflammasome genes and genes involved in the autophagy process, are implicated in Crohn's disease pathogenesis. The aim of this review is to establish how much the diagnostic system can improve, thus increasing the success of Crohn's disease diagnosis. The major expectation for the near future is to be able to anticipate the possible consequences of the disease already in childhood, thus preventing associated complications, and to choose the best treatment for each patient. PMID:23738324
Higashi, Daijiro; Futami, Kitaro; Kojima, Daibo; Futatsuki, Ryo; Ishibashi, Yukiko; Maekawa, Takafumi; Yano, Yutaka; Takatsu, Noritaka; Hirai, Fumihito; Matsui, Toshiyuki; Iwashita, Akinori
Due to an increase in the number of long-term cases of Crohn's disease, the risk of combined cancer in these patients has been assessed in numerous articles. Most of these reports have involved patients with cancer of the large intestine, while cases of cancer of the small intestine combined with Crohn's disease are very rare. We experienced two cases of cancer of the small intestine combined with Crohn's disease. In both cases, the patients had suffered from Crohn's disease for over 10 years and a second operation was performed after a long period without treatment following the first operation, which had achieved a favorable outcome. In both cases of combined cancer, the patients experienced ileus; however, it was difficult to discern this from ileus due to the presence of Crohn's disease. Therefore, making a definitive diagnosis of combined cancer was not possible before surgery, and the definitive diagnosis was obtained based on an intraoperative pathological diagnosis. It is thought that tumor markers transition in a manner parallel to the progression of cancer, providing a clue for cancer diagnosis. In patients with Crohn's disease, there is a pressing need to establish a method for diagnosing cancer of the small intestine at an early stage.
Suskind, David L; Wahbeh, Ghassan; Gregory, Nila; Vendettuoli, Heather; Christie, Dennis
Crohn disease is characterized by chronic intestinal inflammation in the absence of a recognized etiology. Nutritional therapy in the form of exclusive enteral nutrition (EEN) has an established role within pediatric Crohn disease. Following exclusive enteral nutrition's success, many dietary therapies focusing on the elimination of specific complex carbohydrates have been anecdotally reported to be successful. Many of these therapies have not been evaluated scientifically; therefore, we reviewed the medical records of our patients with Crohn disease on the specific carbohydrate diet (SCD). Seven children with Crohn disease receiving the SCD and no immunosuppressive medications were retrospectively evaluated. Duration of the dietary therapy ranged from 5 to 30 months, with an average of 14.6±10.8 months. Although the exact time of symptom resolution could not be determined through chart review, all symptoms were notably resolved at a routine clinic visit 3 months after initiating the diet. Each patient's laboratory indices, including serum albumin, C-reactive protein, hematocrit, and stool calprotectin, either normalized or significantly, improved during follow-up clinic visits. This chart review suggests that the SCD and other low complex carbohydrate diets may be possible therapeutic options for pediatric Crohn disease. Further prospective studies are required to fully assess the safety and efficacy of the SCD, or any other low complex SCDs in pediatric patients with Crohn disease.
Yacoub, Joseph H; Obara, Piotr; Oto, Aytekin
MR enterography is playing an evolving role in the evaluation of small bowel Crohn's disease (CD). Standard MR enterography includes a combination of rapidly acquired T2 sequence, balanced steady-state acquisition, and contrast enhanced T1-weighted gradient echo sequence. The diagnostic performance of these sequences has been shown to be comparable, and in some respects superior, to other small bowel imaging modalities. The findings of CD on MR enterography have been well described in the literature. New and emerging techniques such as diffusion-weighted imaging (DWI), dynamic contrast enhanced MRI (DCE-MRI), cinematography, and magnetization transfer, may lead to improved accuracy in characterizing the disease. These advanced techniques can provide quantitative parameters that may prove to be useful in assessing disease activity, severity, and response to treatment. In the future, MR enterography may play an increasing role in management decisions for patients with small bowel CD; however, larger studies are needed to validate these emerging MRI parameters as imaging biomarkers.
Ursing, B; Alm, T; Bárány, F; Bergelin, I; Ganrot-Norlin, K; Hoevels, J; Huitfeldt, B; Järnerot, G; Krause, U; Krook, A; Lindström, B; Nordle, O; Rosén, A
Seventy-eight patients with active Crohn's disease participated in a randomized, double-blind, cross-over trial. The study comprised two 4-mo period. The purpose was to test the efficacy of metronidazole in comparison with that of sulfasalazine. As the main evaluation criteria the Crohn's Disease Activity Index and plasma levels of orosomucoid were chosen. In the first period no difference in efficacy as measured by Crohn's Disease Activity Index was found between the treatment groups. The reduction of the plasma orosomucoid level was significantly more pronounced in the metronidazole group. The hemoglobin concentration increased more in this group than in the sulfasalazine group, possibly due to a toxic effect of sulfasalazine. The erythrocyte sedimentation rate decreased similarly with both drugs. In 15 patients who had active disease throughout the first period, Crohn's Disease Activity Index decreased significantly in the second period for those who switched to metronidazole, but not for those who switched to sulfasalazine. After crossover, no apparent further change in Crohn's Disease Activity Index occurred in either of the treatment groups among patients who had responded favorably in the first period. The plasma concentration of orosomucoid increased significantly among the patients in the sulfasalazine group but not in the metronidazole group. It is therefore concluded that metronidazole is slightly more effective than sulfasalazine in the treatment of crohn's disease. It is worthwhile switching the drug regimen from sulfasalazine, when it fails, to metronidazole, but not from metronidazole to sulfasalazine.
Adenis, A; Colombel, J F; Lecouffe, P; Wallaert, B; Hecquet, B; Marchandise, X; Cortot, A
We tested the hypothesis that an increased epithelial permeability may affect sites other than the intestine in patients with Crohn's disease by simultaneously evaluating their pulmonary and intestinal permeability. Pulmonary and intestinal permeability were measured by clearance of inhaled technetium-99m diethylene triamine pentacetate (99mTc-DTPA) and by urinary recovery of chromium-51 ethylene diamine tetracetate respectively in 22 patients with Crohn's disease. The half time clearance of 99mTc-DTPA from lung to blood (t1/2LB) was decreased--that is pulmonary permeability increased--in the whole group of patients with Crohn's disease as compared with 13 controls (median 45.5 minutes (8-160) v 85 minutes (34-130) (p less than 0.003)). When analysed separately only patients with active Crohn's disease (n = 15) had a decreased t1/2 lung to blood v controls (42 minutes (8-160) v 85 minutes (34-130) (p less than 0.0025)). Among patients with active Crohn's disease, six were studied again when their disease was quiescent and their t1/2 lung to blood did not differ significantly. The intestinal permeability was increased in the whole group of Crohn's disease patients as compared with 15 controls (5.25% (1.2-24) v 1.7% (0.65-5.75) (p less than 0.0002)). When analysed separately both patients with active and inactive Crohn's disease had increased intestinal permeability v controls (8.1% (1.6-24) and 3.5% (126.96.36.199) v 1.7% (0.65-5.75)) (p less than 0.0001, p = 0.05 respectively). Six patients with active Crohn's disease were studied again when their disease was quiescent and their intestinal permeability decreased significantly p less than 0.04). Pulmonary permeability was increased in patients with Crohn's disease but was not greatly influenced by Crohn's disease activity as opposed to intestinal permeability. The mechanism of this increase is unknown, but may be related in some patients to the presence of an alveolitis. PMID:1612487
Park, Jae Jun; Ye, Byong Duk; Kim, Jong Wook; Park, Dong Il; Yoon, Hyuk; Im, Jong Pil; Lee, Kang Moon; Yoon, Sang Nam; Lee, Heeyoung
Crohn's disease (CD) is a chronic, progressive, and disabling inflammatory bowel disease (IBD) with an uncertain etiopathogenesis. CD can involve any site of the gastrointestinal tract from the mouth to the anus, and is associated with serious complications, such as bowel strictures, perforations, and fistula formation. The incidence and prevalence rates of CD in Korea are still lower compared with those in Western countries, but they have been rapidly increasing during the recent decades. Although there are no definitive curative modalities for CD, various medical and surgical therapies have been applied for the treatment of this disease. Concerning CD management, there have been substantial discrepancies among clinicians according to their personal experience and preference. To suggest recommendable approaches to the diverse problems of CD and to minimize the variations in treatment among physicians, guidelines for the management of CD were first published in 2012 by the IBD Study Group of the Korean Association for the Study of Intestinal Diseases. These are the revised guidelines based on updated evidence, accumulated since 2012. These guidelines were developed by using mainly adaptation methods, and encompass induction and maintenance treatment of CD, treatment based on disease location, treatment of CD complications, including stricture and fistula, surgical treatment, and prevention of postoperative recurrence. These are the second Korean guidelines for the management of CD and will be continuously revised as new evidence is collected. PMID:28239314
Van Ranst, Marc; Joossens, Marie; Joossens, Sofie; Van Steen, Kristel; Pierik, Marieke; Vermeire, Severine; Rutgeerts, Paul
Environmental factors trigger the onset of inflammatory bowel disease (IBD) in genetically predisposed individuals. Exposure to seasonal external factors during the maturation of the immune system is suspected to be an inducing factor for IBD. Some studies suggested an association between the month of birth and the later development of IBD. We studied this putative relationship in a large cohort of Belgian patients with Crohn's disease (CD). Data from 1025 patients born between 1935 and 1990 were collected. Diagnosis of CD was based on generally accepted clinical, endoscopic, and histologic criteria. As a control group, a cohort of 5125 non-IBD patients seen at the same hospital and matched for birth year and sex was used. Odds ratios were calculated using multivariate unconditional logistic regression including the matching variables and allowing for cyclic variation in risk with month of birth. A cyclic pattern described by a 4-month periodic function was observed with peaks in April and August. Moreover, being born in June significantly reduced the risk of developing CD later in life (P = 0.012). In this Belgian cohort, a significant association was found between the month of birth and later development of IBD; a significant reduced risk to develop CD was observed for people born in June. Moreover, environmental yearly reoccurring factors during pregnancy or postpartum might be associated with the occurrence of CD later in life.
Guagnozzi, Danila; Caprilli, Renzo
The pathogenesis of Crohn's disease (CD) is multifactorial and the activation of specific pathways of immunological system is important. In particular, the adhesion molecules (integrins) mediate the selective binding between the leukocytes and the endothelial cells regulating the migration of leukocytes into the normal and inflamed intestine. Selective adhesion molecule inhibitors interfere with the migration of leukocytes to the sites of inflammation by targeting adhesion molecules (alpha4-integrin or alpha4beta7-integrin). Natalizumab is a humanized IgG4 anti-alpha4-integrin monoclonal antibody that inhibits both alpha4beta7-integrin/mucosal addressin-cell adhesion molecule-1 (MadCAM-1) interaction and alpha4beta1/vascular-cell adhesion molecule-1 (VCAM-1) binding. Pooled data from the four studies, analyzed in a Cochrane review, suggest that natalizumab is effective for induction of clinical response and remission in patients with moderately to severely active CD. In particular, natalizumab may be beneficial for patients with active inflammation or chronically active disease despite the use of conventional therapies with high level of C-reactive protein values at baseline time. Nevertheless, many problems about the utilization of natalizumab in CD remain unsolved (such as the high placebo response, the final definition of dosage and timing schedule, the definition of outcomes and the development of adverse events).
Hemminki, K; Li, X; Sundquist, J; Sundquist, K
Patients diagnosed with Crohn disease (CD) are known to be at an increased risk of bowel cancers and lymphoma. CD is an autoimmune disease and we hypothesize that the patients are predisposed to a wider spectrum of cancers. A CD research database was constructed by identifying hospitalized CD patients from the Hospital Discharge Register and cancer patients from the Swedish Cancer Registry. Follow-up of 21 788 CD patients first hospitalized during the years 1964-2004 identified 1424 cancer cases. Standardized incidence ratios (SIRs) were calculated by comparing cancers in CD patients with subjects without CD. In addition to the known sites, many additional sites were in excess in CD patients. These included liver, pancreatic, lung, prostate, testicular, kidney and skin (squamous cell) cancers; nonthyroid endocrine tumors and leukemia. The previously established sites showed the highest SIRs; however, SIRs >2.0 were noted for the novel sites of the liver, testis and kidney. For testicular cancer, the SIR of seminoma was 2.74. Cancer risks were influences by age at first hospitalization for CD but whether the age effects were increasing or decreasing depending on the cancer type. This large study identified many novel subsequent cancers in CD patients.
Weiser, Jessica A; Markowitz, David M; Husain, Sameera; Grossman, Marc E
A 61-year-old man with a 12-year history of quiescent Crohn's disease on mesalamine presented to his gastroenterologist in April 2009, complaining of abdominal cramping, diarrhea, and a 25-lb weight loss over 6 weeks. He did not respond to prednisone 50 mg and 6-mercaptopurine 100 mg daily. Abdominal computed tomography findings revealed diffuse submucosal edema consistent with extensive colitis. Colonoscopy demonstrated diffuse inflammation with erythema, friability, and shallow ulcerations in the rectum and colon. Biopsies were consistent with Crohn's colitis. He was admitted for infliximab infusion for his unremitting diarrhea. Five days before admission, the patient noted mild swelling and redness of the left lower eyelid, which progressed to involve the right lower eyelid with frank pus draining from both eyes. He had no visual impairment or eye pain. Two days before admission, an ophthalmologist prescribed a steroid eyedrop with no relief. He also complained of seropurulent painful skin lesions on his face and scalp, which spread to involve his upper trunk and proximal arms. On admission to the hospital, dermatology, ophthalmology, and infectious disease consultations were obtained to rule out disseminated infection before initiation of infliximab therapy. The patient was afebrile and hemodynamically stable. His oral mucosa was normal. He had prominent bilateral lower eyelid edema, erythema, and superficial erosions with hemorrhagic crusting and frank green purulent drainage from both eyes, with crusting along the lower lash line and bilateral sclera injection (Figure 1). On his scalp, face, trunk, and proximal extremities, he had 25 to 30 erythematous, 4- to 8-mm papulopustules with narrow red halos, some with central necrosis and crusting (Figure 2). Cultures from the purulent ocular drainage and pustules on the trunk and arms were all negative for bacteria, virus, and fungi. Gram stain from the eye drainage showed polymorphonuclear leukocytes without
Rhodes, J M; Cockel, R; Allan, R N; Hawker, P C; Dawson, J; Elias, E
The prevalence of use of oral contraception before the onset of disease was established in 100 consecutive women attending follow up clinics for inflammatory bowel disease. A significant excess of women with Crohn's disease confined to the colon had taken oral contraceptives in the year before developing symptoms (10/16 (63%] compared with women with small-intestinal Crohn's disease (12/49 (24%); p less than 0.02) and women with ulcerative colitis (3/35 (9%); p less than 0.0005). When the patient groups were matched for age and year of onset of disease usage of oral contraception before the onset of disease was still more common among women with isolated colonic Crohn's disease (9/12, 75%) than among those with ulcerative colitis (2/12 (17%); p less than 0.02) and was also more common than would be expected from reported figures for oral contraception in England and Wales (31.4% of women aged under 41; p less than 0.005). A survey of current patient records showed that isolated colonic disease was at least twice as common among women with Crohn's disease (63/218, 29%) compared with men (25/181, 14%; p less than 0.001). These data support the suggestion made previously that oral contraceptives may predispose to a colitis that resembles colonic Crohn's disease. PMID:6421392
Navab, F.; Boyd, C.M.; Diner, W.C.; Subramani, R.; Chan, C.
Twenty-seven patients with Crohn's disease were studied for the presence and location of activity by both early (4 h) and delayed (18-24 h) indium 111 leukocyte imaging. The results were compared with other parameters of disease activity including Crohn's disease activity index, barium studies, and endoscopy. There was a correlation between early images and Crohn's disease activity index (r = 0.78) and between delayed images and index (r = 0.82). Based upon the corresponding Crohn's disease activity index, the sensitivity of early and delayed imaging was 81.0% and 95.2%, respectively. Specificity of early and delayed imaging was 75.0% and 87.0%, respectively. Presence of activity on the early and delayed imaging agreed with activity on barium studies and colonoscopy in approximately 80% of cases. Correlation of location of disease by leukocyte imaging and x-ray was observed in 58.9% of early scans and 55.0% of delayed scans. Correlation of the location of disease by imaging and endoscopy was observed in 71.4% of early and 75.0% of delayed studies. Because of the possibility of occurrence of false-negative results in early images, delayed imaging should always be included in evaluation of disease activity in patients with Crohn's disease who are suspected of having mild activity. Delayed imaging is not required if the early imaging study clearly shows activity.
Liu, Song; Ren, Jianan; Zhao, Yunzhao; Han, Gang; Hong, Zhiwu; Yan, Dongsheng; Chen, Jun; Gu, Guosheng; Wang, Gefei; Wang, Xinbo; Fan, Chaogang; Li, Jieshou
This study was designed to investigate the clinical features of nonthyroidal illness syndrome (NTIS) compared with euthyroid patients in Crohn's disease (CD), to explore the etiology of NTIS in CD, to evaluate the clinical outcomes of NTIS patients, and to inspect the correlation of clinical variables and NTIS, and their ability of differentiating NTIS from euthyroid patients. NTIS has been described for more than 30 years. However, only few studies focused on the relationship between NTIS and CD. The incidence, underlying pathogenesis, clinical outcomes, and correlation with other inflammatory disease severity and nutritional variables of NTIS in CD have not been completely established. Prospectively, 44 CD patients were enrolled. Medical records and various laboratory values (including thyroidal, nutritional, and inflammatory variables) were collected in all participants. The incidence of NTIS in CD was 36.4%. Albumin, Acute Physiology and Chronic Health Evaluation II score, and Crohn's Disease Activity Index score in NTIS group were statistically different from those in euthyroid group. A decreased sum activity of deiodinases and a reduced ratio of TT4/FT4 were observed in NTIS group. Duration of hospitalization was significantly longer for NTIS patients than euthyroid patients. Albumin was confirmed as a protective factor of NTIS in CD. Receiver operating characteristic curve analysis demonstrated the differentiating capacity of albumin, suggesting 37.6 g/L as optimal cut-off value with sensitivity and specificity of 81.3% and 79.2%, respectively. NTIS was a common complication in CD. NTIS patients showed worse nutrition status and clinical outcome, and more critical disease activity and severity compared with euthyroid patients. A hypodeiodination condition and a potential thyroid-hormone-binding dysfunction may play a role in the etiology of NTIS in CD. Albumin was a meaningful protective and distinguishing marker of NTIS in CD.
Otley, Anthony; LeLeiko, Neal; Langton, Christine; Lerer, Trudy; Mack, David; Evans, Jonathan; Pfefferkorn, Marian; Carvalho, Ryan; Rosh, Joel; Griffiths, Anne; Oliva-Hemker, Maria; Kay, Marsha; Bousvaros, Athos; Stephens, Michael; Samson, Charles; Grossman, Andrew; Keljo, David; Markowitz, James; Hyams, Jeffrey
Budesonide (BUD) is being used in pediatric Crohn disease (CD) because it is believed to have the potential to reduce corticosteroid-related toxicity; however, few data are available describing its use. The aim of the present study was to describe BUD use in an inception cohort of pediatric patients with CD. Data were derived from the prospective Pediatric IBD Collaborative Research Group Registry established in 2002 in North America. Use of BUD in children with CD was examined. BUD was used in 119 of 932 (13%) of children with newly diagnosed CD, with 56 of 119 (47%) starting BUD ≤ 30 days of diagnosis (26/56 with ileum and/or ascending colon [IAC] disease). BUD was used as monotherapy (9%), in combination with 5-aminosalicylates (77%), or in combination with immunomodulators (43%). Forty-three percent (24/56) went on to receive conventional corticosteroid at some point following their first BUD course. For the 63 of 119 (53%) who started BUD beyond the diagnosis period, 51 of 63 (81%) also received prednisone, with BUD used as a means of weaning from prednisone in 17 of 63 (27%). Patients with IAC disease who received BUD ≤ 30 days of diagnosis were just as likely to have received conventional corticosteroids by 1 year as were those who did not receive BUD ≤ 30 days of diagnosis. Two-thirds (77/119) of patients received BUD for ≤ 6 months. BUD is being used among pediatric patients newly diagnosed as having CD, although the majority does not have disease limited to the IAC. BUD monotherapy was rare, and further data are required to better define the role of BUD in the treatment of pediatric CD.
Domènech, Eugeni; Mañosa, Míriam; Lobatón, Triana; Cabré, Eduard
Despite the availability of biological drugs and the widespread and earlier use of immunosuppressants, intestinal resection remains necessary in almost half of the patients with Crohn's disease. The development of new mucosal lesions in previously unaffected intestinal segments (a phenomenon known as post-operative recurrence, POR) occur within the first year in up to 80% if no preventive measure is started soon after resectional surgery, leading to clinical manifestations (clinical recurrence) and even needing new intestinal resection (surgical recurrence) in some patients. That is the reason why endoscopic monitoring has been recommended within 6 to 12 months after surgery. Active smoking is the only indisputable risk factor for early POR development. Among several evaluated drugs, only thiopurine and anti-tumor necrosis factor therapy seem to be effective and feasible in the long-term both for preventing or even treating recurrent lesions, at least in a proportion of patients. However, to date, it is not clear which patients should start with one or another drug right after surgery. It is also not well established how and how often POR should be assessed in patients with a normal ileocolonoscopy within the first 12 months.
Yacoub, Joseph H; Oto, Aytekin
Magnetic resonance (MR) enterography has an increasing role in the evaluation of the small bowel in patients with Crohn disease. MR enterography is accurate for disease assessment and can influence the choice of therapy. Functional sequences may increase the role of MR enterography in Crohn disease. Techniques such as high-resolution MR enterography, diffusion-weighted imaging, dynamic contrast-enhanced MR imaging, magnetization transfer, and MR motility imaging may allow better assessment of disease extent, activity, and severity. Quantitative analysis using these advanced techniques as well as the standard techniques may provide methods for evaluating and following the disease in the future.
Tolan, Damian J M; Greenhalgh, Rebecca; Zealley, Ian A; Halligan, Steve; Taylor, Stuart A
Magnetic resonance (MR) enterography is a clinically useful technique for the evaluation of both intraluminal and extraluminal small bowel disease, particularly in younger patients with Crohn disease. MR enterography offers the advantages of multiplanar capability and lack of ionizing radiation. It allows evaluation of bowel wall contrast enhancement, wall thickening, and edema, findings useful for the assessment of Crohn disease activity. MR enterography can also depict other pathologic findings such as lymphadenopathy, fistula and sinus formation, abscesses, and abnormal fold patterns. Even subtle disease manifestations may be detected when adequate distention of the small bowel is achieved, although endoscopic and double-contrast barium small bowel techniques remain superior in the depiction of changes in early Crohn disease (eg, aphthoid ulceration). Further research will be needed to determine whether MR imaging enhancement patterns may reliably help discriminate between active and inactive disease.
Crohns disease is an inflammatory bowel disease that can have a significant impact on the health of those afflicted. The etiology of the disease is unknown, but genetic, environmental, dietary, and immunological factors are thought to be involved. Multiple nutrients can become depleted during active disease due to inadequate intake or malabsorption. Preventing these deficiencies is paramount in the care of those suffering from Crohns disease. Often the traditional treatments (medications) have limited effectiveness and negative side effects that inhibit their use. Enteral nutrition has promising therapeutic benefits, but its use is often limited to the pediatric population due to poor patient acceptability. Omega-3 fatty acids have been investigated for their anti-inflammatory properties as an alternative to traditional care. This article reviews the etiology of Crohns disease, nutritional deficiencies, traditional treatments, and the use of omega-3 fatty acids in the prevention of Crohns recurrence. The results from clinical trials have been conflicting, but a new fish oil preparation that limits the side effects of traditional fish oil therapy shows promise as an adjunctive treatment for Crohns disease. Continued research is needed to validate these findings.
Adler, Jeremy; Dong, Shiming; Eder, Sally J; Dombkowski, Kevin J
Although perianal complications of Crohn disease (CD) are commonly encountered in clinical practice, the epidemiology of perianal CD among populations of children is poorly understood. We sought to characterize the prevalence of perianal disease in a large and diverse population of pediatric patients with CD. We conducted retrospective analyses from a prospective observational cohort, the ImproveCareNow Network (May 2006-October 2014), a multicenter pediatric inflammatory bowel disease quality improvement collaborative. Clinicians prospectively documented physical examination and phenotype classification at outpatient visits. Perianal examination findings and concomitant phenotype change were used to corroborate time of new-onset perianal disease. Results were stratified by age, sex, and race and compared across groups with logistic regression. Cumulative incidence was estimated using Kaplan-Meier analyses and compared between groups with Cox proportional hazard regression models. The registry included 7076 patients with CD (41% girls). Missing/conflicting entries resulted in 397 (6%) patient exclusions. Among the remaining 6679 cases, 1399 (21%) developed perianal disease. Perianal disease was more common among boys (22%) than girls (20%; P = 0.013) and developed sooner after diagnosis among those with later rather than early onset disease (P < 0.001). Perianal disease was also more common among blacks (26%) compared with whites (20%; P = 0.017). Asians with later onset CD developed perianal disease earlier in their disease course (P = 0.01). There was no association between disease location or nutritional status at diagnosis and later development of perianal disease. In this large multicenter collaborative, we found that perianal disease is more common among children with CD than previously recognized. Differences in the development of perianal disease were found across racial and other subgroups. Treatment strategies are needed to prevent
Raftery, Tara; O'Sullivan, Maria
Vitamin D deficiency is common among patients with Crohn's disease. Serum 25-hydroxyvitamin D (25(OH)D) is the best measure of an individual's vitamin D status and current cut-off ranges for sufficiency are debatable. Several factors contribute to vitamin D deficiency in Crohn's disease. These include inadequate exposure to sunlight, inadequate dietary intake, impaired conversion of vitamin D to its active metabolite, increased catabolism, increased excretion and genetic variants in vitamin D hydroxylation and transport. The effects of low 25(OH)D on outcomes other than bone health are understudied in Crohn's disease. The aim of the present review is to discuss the potential roles of vitamin D and the possible levels required to achieve them. Emerging evidence suggests that vitamin D may have roles in innate and adaptive immunity, in the immune-pathogenesis of Crohn's disease, prevention of Crohn's disease-related hospitalisations and surgery, in reducing disease severity and in colon cancer prevention. The present literature appears to suggest that 25(OH)D concentrations of ≥75 nmol/l may be required for non-skeletal effects; however, further research on optimal levels is required.
Björnsson, Bergthor; Ignatova, Simone; Sandström, Per; Ekstedt, Mattias
Littoral cell angioma is a rare vascular tumor of the spleen. The pathogenesis is unknown but the lesion is associated with several malignancies and immunological disorders. The diagnosis requires histopathological examination. The malignant potential of this lesion is unknown, which is why splenectomy is recommend for all cases. Symptomatic cases generally suffer from hypersplenism and pyrexia. A previously healthy 20-year-old female was diagnosed with colonic Crohn's disease; as part of the work-up a magnetic resonance enterography was performed which showed multiple signal changes of the spleen. The patient reported chronic abdominal pain in the left upper quadrant, malaise, and fever. The unknown splenic lesions prompted a laparoscopic splenectomy; pathology revealed a littoral cell angioma. The abdominal pain and malaise remitted but the fever persisted one year despite adequate treatment of the patient's Crohn's disease. Littoral cell angioma is associated with immune-dysregulation including Crohn's disease with several reported cases. Signs and symptoms of hypersplenism and splenic lesions on imaging should raise suspicion of littoral cell angioma in patients with Crohn's disease. Magnetic resonance enterography to assess disease severity in Crohn's disease may provide an opportunity to study the prevalence and natural history of this rare splenic tumor. PMID:25705528
Tibble, J; Teahon, K; Thjodleifsson, B; Roseth, A; Sigthorsson, G; Bridger, S; Foster, R; Sherwood, R; Fagerhol, M; Bjarnason, I
BACKGROUND AND AIMS—Assessing the presence and degree of intestinal inflammation objectively, simply, and reliably is a significant problem in gastroenterology. We assessed faecal excretion of calprotectin, a stable neutrophil specific marker, as an index of intestinal inflammation and its potential use as a screening test to discriminate between patients with Crohn's disease and those with irritable bowel syndrome. METHODS—The validity of faecal calprotectin as a marker of intestinal inflammation was assessed in 22 patients with Crohn's disease (35 studies) by comparing faecal excretions and concentrations using four day faecal excretion of 111indium white cells. A cross sectional study assessed the sensitivity of faecal calprotectin concentration for the detection of established Crohn's disease (n=116). A prospective study assessed the value of faecal calprotectin in discriminating between patients with Crohn's disease and irritable bowel syndrome in 220 patients referred to a gastroenterology clinic. RESULTS—Four day faecal excretion of 111indium (median 8.7%; 95% confidence interval (CI) 7-17%; normal <1.0%) correlated significantly (p<0.0001) with daily (median ranged from 39 to 47 mg; normal <3 mg; r=0.76-0.82) and four day faecal calprotectin excretion (median 101 mg; 95% CI 45-168 mg; normal <11 mg; r=0.80) and single stool calprotectin concentrations (median 118 mg/l; 95% CI 36-175 mg/l; normal <10 mg/l; r=0.70) in patients with Crohn's disease. The cross sectional study showed a sensitivity of 96% for calprotectin in discriminating between normal subjects (2 mg/l; 95% CI 2-3 mg/l) and those with Crohn's disease (91 mg/l; 95% CI 59-105 mg/l). With a cut off point of 30 mg/l faecal calprotectin has 100% sensitivity and 97% specificity in discriminating between active Crohn's disease and irritable bowel syndrome. CONCLUSION—The calprotectin method may be a useful adjuvant for discriminating between patients with Crohn's disease and
Greenstein, Robert J
Although Crohn's disease is considered to be autoimmune in origin, there is increasing evidence that it may have an infectious cause. The most plausible candidate is Mycobacterium avium subspecies paratuberculosis (MAP). Intriguingly, Koch's postulates may have been fulfilled for MAP and Crohn's disease, even though they still have not been met for Mycobacterium leprae and leprosy. In animals MAP causes Johne's disease, a chronic wasting intestinal diarrhoeal disease evocative of Crohn's disease. Johne's disease occurs in wild and domesticated animals, including dairy herds. Viable MAP is found in human and cow milk, and is not reliably killed by standard pasteurisation. MAP is ubiquitous in the environment including in potable water. Since cell-wall-deficient MAP usually cannot be identified by Ziehl-Neelsen staining, identification of MAP in human beings requires culture or detection of MAP DNA or RNA. If infectious in origin, Crohn's disease should be curable with appropriate antibiotics. Many studies that argue against a causative role for MAP in Crohn's disease have used antibiotics that are inactive against MAP. However, trials that include macrolide antibiotics indicate that a cure for Crohn's disease is possible. The necessary length of therapy remains to be determined. Mycobacterial diseases have protean clinical manifestations, as does Crohn's disease. The necessity of stratifying Crohn's disease into two clinical manifestations (perforating and non-perforating) when interpreting the results of antibiotic therapy is discussed. Rational studies to evaluate appropriate therapies to cure Crohn's disease are proposed.
Lapaquette, Pierre; Brest, Patrick; Hofman, Paul; Darfeuille-Michaud, Arlette
Crohn's disease is a complex multifactor diseases that occur in individuals with genetic predisposition in whom environmental and microbial triggers cause a deleterious chronic immune response. Susceptibility to Crohn's disease is influenced by common variants at many loci. Genetic studies have emphasized the role of host susceptibility in inflammatory bowel disease onset with the identification of about 100 risk loci, most of which encode proteins involved in immunity, host defense against microbes, and gut homeostasis. In this review, we focus on susceptibility genes related to autophagy in the etiology of Crohn's disease (CD) and their complex interplay with the gut microbiota, as illustrated by the relationship between immunity-related GTPase family M alleles, microRNA, and xenophagy in CD predisposition.
Crocker, Justin A; Yu, Huimin; Conaway, Mark; Tuskey, Anne G; Behm, Brian W
The rate of narcotic misuse in the inflammatory bowel disease population is not well studied. The primary aim of this study was to determine in Crohn's disease (CD) whether a concurrent functional gastrointestinal disorder (FGID) was associated with increased rates of chronic narcotic use. Second, we aimed to identify potential risk factors for narcotic misuse. A retrospective chart review of patients with CD followed at the University of Virginia's Gastroenterology Clinic from 2006 to 2011 was performed. The prescription monitoring program was accessed to confirm narcotic prescription filling histories. Narcotic misuse was defined as narcotic prescriptions filled from 4 or more prescribers and at 4 or more different pharmacies. Nine hundred thirty-one patients with CD were included in the study cohort. Eighty-seven (9.3%) patients were identified as having a concurrent FGID, and 192 (20%) were taking chronic narcotics. Patients with FGID were more likely to be taking chronic narcotics (44% versus 18%, P < 0.001). Thirty-seven percent (32/87) of patients with an FGID were misusing narcotics, compared with 9.6% (81/844) (P < 0.0001). Multivariate logistic regression demonstrated a significant association of misuse in patients with a concurrent FGID (odds ratio = 3.33, 95% confidence interval, 1.87-5.93). Twenty percent of patients with CD were using chronic narcotics with higher rates in those with FGID. Using the prescription monitoring program, a significant proportion of patients with CD with an FGID were misusing narcotics. We would recommend screening for narcotic misuse in patients with CD with a concomitant FGID and consider using prescription monitoring programs to identify others at risk for misuse.
Hvas, Christian Lodberg; Dahlerup, Jens Frederik; Jacobsen, Bent Ascanius; Ljungmann, Ken; Qvist, Niels; Staun, Michael; Tøttrup, Anders
A fistula is defined as a pathological connection between the intestine and an inner (bladder or other intestine) or outer (vagina or skin) epithelial surface. Fistulas are discovered in up to 25% of all Crohn's disease patients during long-term follow-up examinations. Most are perianal fistulas, and these may be classified as simple or complex. The initial investigation of perianal fistulas includes imaging (MRI of the pelvis and rectum), examination under anaesthesia (EUA) with digital imaging, endoscopy, probing and anal ultrasound. Non-perianal fistulas require contrast imaging and/or CT/MRI for complete anatomical definition. Any abscess should be drained, and the disease extent throughout the entire gastrointestinal tract should be evaluated. Treatment goals for perianal fistulas include reduced fistula secretion or none, evaluated by clinical examination; the absence of abscesses; and patient satisfaction. MR imaging is required to demonstrate definitive fistula closure. Fistulotomy is considered for simple perianal fistulas. In complex perianal fistulas, antibiotics and azathioprine or 6-mercaptopurine, which are often combined with a loose seton, constitute the first-line medical therapy. In cases with persistent secretion, infliximab at 5 mg/kg is given at weeks 0, 2, and 6 and subsequently every 8 weeks. Adalimumab may improve fistula response in both infliximab-naïve patients and following infliximab treatment failure. Local therapy with fibrin glue or fistula plugs is rarely effective. Definitive surgical closure of perianal fistulas using an advancement flap may be attempted, but this procedure is associated with a high risk of relapse. Colostomy and proctectomy are the ultimate surgical treatment options for fistulas. Intestinal resection is almost always needed for the closure of symptomatic non-perianal fistulas.
Sharma, Raju; Madhusudhan, Kumble S; Ahuja, Vineet
Intestinal tuberculosis is a common clinical problem in India. The clinical features of this disease are nonspecific and can be very similar to Crohn's disease. Radiological evaluation of the small bowel has undergone a paradigm shift in the last decade. This long tubular organ that has traditionally been difficult to evaluate can now be well-visualized by some innovative imaging and endoscopic techniques. This article highlights the state-of-the-art evaluation of ulceroconstrictive diseases of the bowel and provides recommendations for the differentiation of intestinal tuberculosis from Crohn's disease. PMID:27413261
Caprilli, R; Gassull, M A; Escher, J C; Moser, G; Munkholm, P; Forbes, A; Hommes, D W; Lochs, H; Angelucci, E; Cocco, A; Vucelic, B; Hildebrand, H; Kolacek, S; Riis, L; Lukas, M; de Franchis, R; Hamilton, M; Jantschek, G; Michetti, P; O'Morain, C; Anwar, M M; Freitas, J L; Mouzas, I A; Baert, F; Mitchell, R; Hawkey, C J
This third section of the European Crohn's and Colitis Organisation (ECCO) Consensus on the management of Crohn's disease concerns postoperative recurrence, fistulating disease, paediatrics, pregnancy, psychosomatics, extraintestinal manifestations, and alternative therapy. The first section on definitions and diagnosis reports on the aims and methods of the consensus, as well as sections on diagnosis, pathology, and classification of Crohn's disease. The second section on current management addresses treatment of active disease, maintenance of medically induced remission, and surgery of Crohn's disease. PMID:16481630
Oda, Masahiro; Kitasaka, Takayuki; Furukawa, Kazuhiro; Watanabe, Osamu; Ando, Takafumi; Goto, Hidemi; Mori, Kensaku
The purpose of this paper is to present a CAD prototype system for Crohn's disease. Crohn's disease causes inflammation or ulcers of the gastrointestinal tract. The number of patients of Crohn's disease is increasing in Japan. Symptoms of Crohn's disease include intestinal stenosis, longitudinal ulcers, and fistulae. Optical endoscope cannot pass through intestinal stenosis in some cases. We propose a new CAD system using abdominal fecal tagging CT images for efficient diagnosis of Crohn's disease. The system displays virtual unfolded (VU), virtual endoscopic, curved planar reconstruction, multi planar reconstruction, and outside views of both small and large intestines. To generate the VU views, we employ a small and large intestines extraction method followed by a simple electronic cleansing method. The intestine extraction is based on the region growing process, which uses a characteristic that tagged fluid neighbor air in the intestine. The electronic cleansing enables observation of intestinal wall under tagged fluid. We change the height of the VU views according to the perimeter of the intestine. In addition, we developed a method to enhance the longitudinal ulcer on views of the system. We enhance concave parts on the intestinal wall, which are caused by the longitudinal ulcer, based on local intensity structure analysis. We examined the small and the large intestines of eleven CT images by the proposed system. The VU views enabled efficient observation of the intestinal wall. The height change of the VU views helps finding intestinal stenosis on the VU views. The concave region enhancement made longitudinal ulcers clear on the views.
Liu, Song; Ding, Jie; Wang, Meng; Wang, Gefei; Wu, Xiuwen; Feng, Min; Song, Peng; Ren, Jianan; Guan, Wenxian
Occupational factors have been suggested as possible elements in the etiology of Crohn's disease, although evidences have not been fully obtained. This study is to investigate possible associations between occupation and development of Crohn's disease. This prospective study was carried out in two major hospitals during January 2010 and December 2014. Demographic and clinical data were collected for the calculation of standard incidence ratios and 95% confidence intervals by occupation. A total of 401 patients with Crohn's disease were recruited into this study. Participants were distributed into 8 major occupational groups, among which "professionists" (17.7%), "service and sales" (18.7%) and "unclassified individuals" (mainly students) (20.2%) took up the most proportions. Increased standard incidence ratios were found in "service and sales" (2.526±0.135, 95% CI: 1.939-3.290), "professionists" (4.216±0.142, 95% CI: 3.194-5.565), and most significantly, in "administrative staffs" (5.476±0.170, 95% CI: 3.926-7.639). In contrast, decreased standard incidence ratios for Crohn's disease were observed in the category of "workers in agriculture, forestry, animal husbandry, fishery and water conservancy" (0.088±0.146, 95% CIs: 0.066-0.117). Occupational elements are implicated in the likelihood of development of Crohn's disease. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
In the early 90s American authors estimated that if a theoretical new drug was introduced that was capable of changing the natural course of the disease and reducing direct non-drug medical costs (including hospitalisation and surgery) by 20%, despite doubling the overall drugs bill, there would still be a reduction in total direct medical costs of Crohn's disease by 13%. Infliximab proved to be efficacious in reducing and maintaining remission in moderate to severe active Crohn's disease and/or fistulising Crohn's disease. A higher acquisition cost still remains its major limitation. Currently only the use of infliximab in case of treatment for flares seems to be cost-effective. However, this statement may be modified in the near future. PMID:26759625
Carratú, Pierluigi; Dragonieri, Silvano; Nocerino, Maria Cristina; Trabucco, Senia Maria Rosaria; Lacedonia, Donato; Parisi, Giuseppe; Resta, Onofrio
A 29 year-old-man with Crohn's disease, who developed diffuse pulmonary infiltrates and hypoxemia two months following oral administration of mesalazine, was examined. Clinical findings and computed tomography were suggestive of, and lung histology was diagnostic of, bronchiolitis obliterans organizing pneumonia, also known as cryptogenic organizing pneumonia. Although the data did not allow for definitive conclusions, they did suggest that the pulmonary disease was an extraintestinal manifestation of Crohn's disease, rather than an adverse reaction to mesalazine. In fact, the patient showed clinical, radiological and functional improvements, despite the treatment with mesalazine and the withdrawal of steroid therapy.
Mahdi, Batool Mutar
Crohn's disease (CD) is the main type of chronic inflammatory bowel disease of unknown etiology. Evidence from family and twin studies suggests that genetics plays a significant role in predisposing an individual to develop Crohn's disease. A susceptibility locus for Crohn's disease has been mapped 3 to chromosome 16: a frameshift variant and two missense variants of NOD2, encoding a member of the Apaf-1/Ced-4 superfamily of apoptosis regulators which is expressed in hematopoietic compartment cells and intestinal epithelial cells as well as in paneth cells, where NOD2 may play an important role in the pathogenesis of Crohn disease in the gastrointestinal system. This leads to alteration the structure of either the leucine-rich repeat domain of the protein or the adjacent region. NOD2 activates nuclear factor NF-kB; this activating function is regulated by the carboxy-terminal leucine-rich repeat domain, which has two functions, first an inhibitory role and also acts as an intracellular receptor for components of microbial pathogens. Thus, NOD2 gene product confers susceptibility to Crohn's disease by altering the recognition of these components and/or by over-activating NF-kB in intestinal epithelial cells as well as in paneth cells. Further confirmation of a genetic predisposition comes from studies of the association between the human leukocyte antigen (HLA) system and CD. The immunogenetic predisposition may be considered an important requirement for the development of CD, as several alleles of human major histocompatibility complex had an association with CD. Although it is difficult to estimate the importance of this region in determining overall genetic susceptibility in a population, studies of HLA allele sharing within families suggest that this region contributes between 10% and 33% of the total genetic risk of Crohn's disease. PMID:26288728
Tsukui, Hidenori; Koinuma, Koji; Morimoto, Mitsuaki; Horie, Hisanaga; Lefor, Alan Kawarai; Kagaya, Yuka; Takahashi, Haruo; Yano, Tomonori; Matsubara, Daisuke; Yamamoto, Hironori; Sata, Naohiro
We report the case of a patient with Crohn's disease who initially presented with a ceco-urachal fistula. The patient was a 31-year-old female who underwent an appendectomy 6 years before presenting to our institution. She had a one-year history of diarrhea, and had recently developed polyuria and a sensation of residual urine. She was admitted with fever and lower abdominal pain. Endoscopy and computed tomography revealed a ceco-urachal fistula, which was consistent with Crohn's disease. An urachal resection was performed, which included partial cystectomy and ileocecal resection. A ceco-urachal fistula is a rare initial symptom of Crohn's disease. During the surgical management of such cases, it is necessary to resect the urachus, the affected portion of the bladder, the fistula, and the affected part of the digestive tract in order to avoid recurrence.
Freeman, Hugh J; Davis, Jennifer E; Prest, Marcia E; Lawson, Edward J
A 37-year-old man with extensive Crohn's disease of the stomach, small and large intestine for almost a decade developed respiratory symptoms and radiological findings suggestive of pneumonia that failed to resolve with antibiotic treatment. Computed tomography scanning of his lungs showed extensive changes with cavitated parenchymal nodules. Histological evaluation of an open lung biopsy showed granulomatous bronchiolitis and pulmonary necrobiosis. Treatment with steroids and immunosuppression resulted in complete resolution of his clinical symptoms of pneumonia and abnormal computed tomography imaging changes. Granulomatous bronchiolitis and necrobiotic nodules may be a manifestation of Crohn's disease in the absence of microbial agents, including mycobacteria or fungal agents. While a multiplicity of complex pulmonary changes may occur in Crohn's disease, their clinical recognition and precise pathological definition may be particularly important if treatment with a biological agent, such as infliximab, is being considered.
Habal, Flavio; Huang, Vivian
A 46-year-old female patient with terminal ileum Crohn's disease and ankylosing spondylitis presented with recurrent angioedema and urticaria. Investigations ruled out hereditary angioedema, and environmental or food allergen triggers. She was diagnosed with chronic idiopathic urticaria with angioedema, and was treated with a trial of intravenous immunoglobulin immunotherapy, danazol, prednisone and hydroxyzine. Due to ongoing bowel and arthritic complaints, she was started on infliximab infusions and within 2 treatments, she had complete resolution of the angioedema and urticaria, as well as of the bowel and arthritic symptoms. Unfortunately she developed allergic reactions to the infliximab and was switched to another anti-tumor necrosis factor (TNF)-α agent, adalimumab. Since then, she has had no further angioedema or urticaria, and her Crohn's disease has been quiescent. This is the first known case report of chronic idiopathic urticaria with angioedema coexistent with Crohn's disease that was successfully treated with anti-TNF-α agents.
Juste, Ramón A
Crohn's disease (CD) is a well known chronic pathological condition whose aetiology has remained unrecognized for nearly a century. Complex immune mechanisms in a specific genetic background causing an abnormal local inflammatory response are thought to be directly responsible for the clinical picture, but no external factor triggering such host responses has been identified. Humans lose the capability of breaking down milk lactose early in life and, afterwards, ingestion of large amounts of lactose causes a transient digestive illness known as lactose intolerance. Some human populations developed mutations for lactase persistence in adulthood that allowed better exploiting a product, milk, from not food-competitive domesticated species. This adaptation to dairy farming could have had as a collateral effect the exposure of human populations to a ruminant parasite with the ability to cause chronic inflammation in the intestine. Humans with a genetic susceptibility might develop a similar inflammatory disease caused by a defect in a highly conserved innate immunity mechanism. Data from different published sources regarding by country CD and type I diabetes incidence, lactose intolerance, livestock population, food production, Gross National Income and human population were submitted to Pearson and Kendall correlation, multiple regression and principal components analyses. Multiple regressions were also applied to a published 20-year time series for CD incidence in Japan. These analyses showed a strong association between country incidence of CD and frequency of lactase persistence as well as other ruminant production and consumption variables that further supports the meaning of those observations. Association of these variables with higher per capita income suggests that IBD incidence would be a side-effect of an otherwise highly successful adaptation. The evolutionarily plausible framework provided by this association with the species suffering a similar
Oda, Masahiro; Kitasaka, Takayuki; Furukawa, Kazuhiro; Watanabe, Osamu; Ando, Takafumi; Goto, Hidemi; Mori, Kensaku
The purpose of this paper is to present a new method to detect ulcers, which is one of the symptoms of Crohn's disease, from CT images. Crohn's disease is an inflammatory disease of the digestive tract. Crohn's disease commonly affects the small intestine. An optical or a capsule endoscope is used for small intestine examinations. However, these endoscopes cannot pass through intestinal stenosis parts in some cases. A CT image based diagnosis allows a physician to observe whole intestine even if intestinal stenosis exists. However, because of the complicated shape of the small and large intestines, understanding of shapes of the intestines and lesion positions are difficult in the CT image based diagnosis. Computer-aided diagnosis system for Crohn's disease having automated lesion detection is required for efficient diagnosis. We propose an automated method to detect ulcers from CT images. Longitudinal ulcers make rough surface of the small and large intestinal wall. The rough surface consists of combination of convex and concave parts on the intestinal wall. We detect convex and concave parts on the intestinal wall by a blob and an inverse-blob structure enhancement filters. A lot of convex and concave parts concentrate on roughed parts. We introduce a roughness value to differentiate convex and concave parts concentrated on the roughed parts from the other on the intestinal wall. The roughness value effectively reduces false positives of ulcer detection. Experimental results showed that the proposed method can detect convex and concave parts on the ulcers.
Toelen, C; Huyghe, M
Gallstone ileus is a rare complication of cholelithiasis. Only 0,3-0,5% of all patients with gallstones will eventually suffer from this condition. It is well known that there is an increased prevalence of gallstones among patients with Crohn's disease, but gallstone ileus remains even in these patients an unfrequent condition. Because of the rarity of this disease and its presentation as an intestinal (sub)obstruction, mostly without biliary symptoms, diagnosis and surgical treatment are often delayed. We report the case of a 75-year-old woman with a long history of Crohn's disease presenting with intermittent symptoms of intestinal obstruction since several weeks. Symptoms were thought to be due to recurrence of Crohn's disease, but the patient did not respond to steroid therapy. Resection of the diseased ileocolic segment was performed and a large impacted stone was detected proximal of the stenotic segment. With this case report we want to emphasize how easily diagnosis of gallstone ileus can be missed, especially in Crohn's patients and we would like to discuss the different treatment options.
Manerowska, Anna; Dadalski, Maciej; Socha, Piotr; Mulawka, Jan
The primary objective of this article is to find a new, more effective method of diagnosis of Crohn's disease. Having created the database on this disease we wanted to find the most suitable classification models. We used the algorithms with their implementations stored in R environment. Having carried out the investigations we have reached results interesting for clinical practice.
Gelphi, A. P.
The author reviews clinical patterns of inflammatory bowel disorders, establishes a perspective for recognizing ulcerative colitis, ulcerative proctitis, and Crohn's disease in relation to other bowel inflammations, and suggests some epidemiologic strategies for studying etiology, pathogenesis, and natural history of the diseases. (MJB)
Gelphi, A. P.
The author reviews clinical patterns of inflammatory bowel disorders, establishes a perspective for recognizing ulcerative colitis, ulcerative proctitis, and Crohn's disease in relation to other bowel inflammations, and suggests some epidemiologic strategies for studying etiology, pathogenesis, and natural history of the diseases. (MJB)
Alliet, P; Desimpelaere, J; Hauser, B; Janssens, E; Khamis, J; Lewin, M; De Greef, E; Smets, F; Paquot, I; Veereman, G; Souverijns, G
Magnetic Resonance enterography (MRE) is an imaging modality avoiding ionizing radiation and the discomfort associated with enteroclysis. The results of MRE at diagnosis in the patients of the Belgian pediatric Crohn registry (Belcro) are compared to endoscopical and histological results. Results of MRE, endoscopy and histology were obtained from the medical charts and assigned to one of the following segments: jejunum, ileum, ascending colon, transverse colon, descending colon or rectosigmoid. MRE images were reviewed in a blinded way by 4 radiologists with specific interest in pediatric MRE. From the Belcro registry, twenty-two patients underwent a MRE during their work-up for Crohn disease. The results of endoscopy, histology and MRE were concordant (either all negative or positive) in the ileum in 16/18 patients and in the rectosigmoid, descending colon, transverse colon and ascending colon in resp 9, 8, 8 and 8/22 patients. In the non-concordant cases (MRE colon negative but endoscopy and/or histology positive), MRE could not reflect the subtle endoscopic or histologic lesions such as erosions that were described.In 4 cases where ileocaecal valve intubation was impossible ileal MRE findings were abnormal. MRE detected ileal stenosis, jejunal lesions and fistula in resp 4/22, 3/22 en 2/22 patients. The 100% and 75% interobserver agreement was resp 50-82% and 773-100% according to the different intestinal segments. MRE is a promising imaging modality avoiding radiation in Crohn disease. It should probably become the technique of first choice for the evaluation of extensive small bowel disease in children with Crohn disease.
Aytac, Erman; Dietz, David W; Ashburn, Jean; Remzi, Feza H
Patients with Crohn's disease have a higher failure rate after ileal pouch surgery compared with their counterparts with ulcerative colitis. We hypothesized that risk of continent ileostomy failure can be stratified based on the timing of Crohn's disease diagnosis and aimed to assess long-term outcomes. This was a retrospective cohort study. The investigation took place in a high-volume, specialized colorectal surgery department. Patients with Crohn's disease who underwent continent ileostomy surgery between 1978 and 2013 were evaluated. Functional outcomes, postoperative complications, requirement of revision surgery, and continent ileostomy failure were analyzed. There were 48 patients (14 male patients) with a median age of 33 years at the time of continent ileostomy creation. Crohn's disease diagnosis was before continent ileostomy (intentional) in 15 or made in a delayed fashion at a median 4 years after continent ileostomy in 33 patients. Median follow-up was 19 years (range, 1-33 y) after index continent ileostomy creation. Major and minor revisions were performed in 40 (83%) and 13 patients (27%). Complications were fistula (n = 20), pouchitis (n = 16), valve slippage (n = 15), hernia (n = 9), afferent limb stricture (n = 9), difficult intubation (n = 8), incontinence (n = 7), bowel obstruction (n = 7), valve stricture (n = 5), leakage (n = 4), bleeding (n = 3), and valve prolapse (n = 3). Median Cleveland global quality-of-life score was 0.8. Continent ileostomy failure occurred in 22 patients (46%). Based on Kaplan-Meier estimates, continent ileostomy survival was 48 % (95% CI, 33%-63%) at 20 years. Continent ileostomy failure was similar regardless of timing of diagnosis of Crohn's disease (p = 0.533). This study was limited by its retrospective and nonrandomized nature. Outcomes of continent ileostomy in patients with Crohn's disease are poor, regardless of the timing of diagnosis. Very careful consideration should be given by both the surgeon and the
Levesque, Barrett G; Cipriano, Lauren E; Chang, Steven L; Lee, Keane K; Owens, Douglas K; Garber, Alan M
The cost effectiveness of alternative approaches to the diagnosis of small-bowel Crohn's disease is unknown. This study evaluates whether computed tomographic enterography (CTE) is a cost-effective alternative to small-bowel follow-through (SBFT) and whether capsule endoscopy is a cost-effective third test in patients in whom a high suspicion of disease remains after 2 previous negative tests. A decision-analytic model was developed to compare the lifetime costs and benefits of each diagnostic strategy. Patients were considered with low (20%) and high (75%) pretest probability of small-bowel Crohn's disease. Effectiveness was measured in quality-adjusted life-years (QALYs) gained. Parameter assumptions were tested with sensitivity analyses. With a moderate to high pretest probability of small-bowel Crohn's disease, and a higher likelihood of isolated jejunal disease, follow-up evaluation with CTE has an incremental cost-effectiveness ratio of less than $54,000/QALY-gained compared with SBFT. The addition of capsule endoscopy after ileocolonoscopy and negative CTE or SBFT costs greater than $500,000 per QALY-gained in all scenarios. Results were not sensitive to costs of tests or complications but were sensitive to test accuracies. The cost effectiveness of strategies depends critically on the pretest probability of Crohn's disease and if the terminal ileum is examined at ileocolonoscopy. CTE is a cost-effective alternative to SBFT in patients with moderate to high suspicion of small-bowel Crohn's disease. The addition of capsule endoscopy as a third test is not a cost-effective third test, even in patients with high pretest probability of disease. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
Felder, J B; Adler, D J; Korelitz, B I
Steroid therapy is often avoided in the Crohn's disease patient with a palpable abdominal mass, for fear of dissemination of infection, should the mass prove to contain an abscess. In the present study, 24 patients with Crohn's disease and a palpable abdominal mass were treated with high dose steroids. In 15, the mass resolved completely and, in another nine, it decreased in size by at least 50%. Fourteen of 24 patients eventually required resection for persistence or recurrence of Crohn's disease activity with or without the abdominal mass, but in all the operation was performed electively. At least eight patients never required resection during a mean follow-up period of 40 months. In 13 patients, the mass was later proved to actually contain an abscess cavity. No complications attributable to steroid therapy were seen in either the operative or nonoperative group. Clinicians should not fear using high dose ACTH/corticosteroids to treat severe Crohn's disease with an abdominal mass, if indicated, as it is both safe and effective whether an abscess cavity is present or not.
Soyer, Philippe; Hristova, Lora; Boudghène, Frank; Hoeffel, Christine; Dray, Xavier; Laurent, Valérie; Fishman, Elliot K; Boudiaf, Mourad
The aim of this study was to analyze the clinical, pathological, and CT-enterography findings of small bowel adenocarcinomas in Crohn disease patients. Clinical, histopathological, and imaging findings were retrospectively evaluated in seven Crohn disease patients with small bowel adenocarcinoma. CT-enterography examinations were reviewed for morphologic features and location of tumor, presence of stratification, luminal stenosis, proximal dilatation, adjacent lymph nodes, and correlated with findings at histological examination. The tumor was located in the terminal (n = 6) or distal (n = 1) ileum. On CT-enterography, the tumor was visible in five patients, whereas two patients had no visible tumor. Four different patterns were individualized including small bowel mass (n = 2), long stenosis with heterogeneous submucosal layer (n = 2), short and severe stenosis with proximal small bowel dilatation (n = 2), and sacculated small bowel loop with irregular and asymmetric circumferential thickening (n = 1). Stratification, fat stranding, and comb sign were present in two, two, and one patients, respectively. Identification of a mass being clearly visible suggests strongly the presence of small bowel adenocarcinoma in Crohn disease patients but adenocarcinoma may be completely indistinguishable from benign fibrotic or acute inflammatory stricture. Knowledge of these findings is critical to help suggest the diagnosis of this rare but severe complication of Crohn disease.
Chiorean, Liliana; Schreiber-Dietrich, Dagmar; Braden, Barbara; Cui, XinWu; Dietrich, Christoph F
The intestinal wall can be visualized using high resolution transabdominal ultrasound (TUS). TTUS measurement of the bowel wall thickness has been described in adults but data are lacking in children. The purpose of this prospective study was to sonographically investigate bowel wall thickness in healthy children and children with Crohn's disease. TUS (5-15 MHz) of the intestine was performed in 58 healthy children (age range 3 to 16 years) and in 30 children with Crohn's disease (age range 8 to 17 years). The following regions were assessed and bowel wall thickness measured: terminal ileum, cecum, right flexure, and sigmoid colon. In patients with Crohn's disease, the involved region was additionally assessed regarding length of involved segment and sonographic signs of transmural inflammation and fistula. TUS allowed adequate measurement of bowel wall thickness in all 58 healthy children (100%) and in all 30 Crohn's disease patients (100%). The bowel wall thickness significantly differed between groups. Bowel wall thickness (mean +/- SD) in all segments was less then 2 mm in all healthy children (1.0+/-0.1 mm terminal ileum, 1.1+/-0.1 mm cecum, 1.1+/-0.1 mm right flexure, and 1.3+/-0.1 mm sigmoid colon). In Crohn's disease patients, bowel wall thickness was ≥ 3 mm in the ileocecal region and was significantly increased (5.1+/-1.9 mm) compared to the healthy children. The mean length of involved segment was 15+/-6.5 cm [5 - 30 cm]. Additional findings in Crohn's disease patients were: transmural inflamation (3/30), interenteric fistula (3/30), gastrocolic fistula (1/30) and vesicoenteric fistula (1/30). Similar to adults, normal bowel wall thickness in children is always less than 2 mm. In all patients with Crohn's disease, increased bowel wall thickness could be detected. TUS is a helpful tool in the diagnosis and assessment of activity and complications in Crohn's disease.
Ahmed Ali, Usama; Martin, Sean T; Rao, Abhishek D; Kiran, Ravi P
Immunosuppressive agents are essential in the management of Crohn's disease. Their safety before surgery, however, is still controversial. The aim of this study is to evaluate whether the preoperative use of immunosuppressive agents is associated with increased postoperative complications in Crohn's disease. A literature search of PubMed, EMBASE, and The Cochrane Library was undertaken in February 2013. All studies describing postoperative outcomes of patients undergoing bowel resections for Crohn's disease were included if they reported data comparing patients on preoperative immunosuppressive agents with an appropriate control group. All immunosuppressive agents used to manage Crohn's disease were studied. The main outcomes measured were total overall complications and total infectious complications. Twenty-one eligible studies (20 retrospective and 1 prospective) with 6899 patients were included. When individual studies were examined, only 2/14 (14%), 4/13 (31%), and 1/8 (13%) studies found an association between postoperative complications and preoperative anti-tumor necrosis factor agents, corticosteroids, and thiopurines. In meta-analyses, patients on anti-tumor necrosis factor agents (risk ratio, 1.29; 95% CI, 1.07-1.55), and corticosteroids (risk ratio, 1.55; 95% CI, 1.23-1.95) were found to have a higher risk of postoperative infectious complications. The use of anti-tumor necrosis factor agents was also significantly associated with wound infection (risk ratio, 1.62; 95% CI, 1.12-2.34) and septic shock (risk ratio, 1.81; 95% CI, 1.03-3.17). There was no association between the use of thiopurines or combined immunomodulator drugs and postoperative complications. Most studies were retrospectively designed, and there were large variations in the patient populations and outcome definitions. Patients with Crohn's disease on preoperative immunosuppressive agents are at higher risk for complications. Both corticosteroids and anti-tumor necrosis factor agents may
Alexander, David B; Iigo, Masaaki; Abdelgied, Mohamed; Ozeki, Keiji; Tanida, Satoshi; Joh, Takashi; Takahashi, Satoru; Tsuda, Hiroyuki
A 22-year-old male suffering from abdominal pain, repeated diarrhea, and weight loss visited the Digestive Disease Department of Nagoya City University Hospital on 19 December 2011. He was hospitalized and diagnosed with Crohn's colitis. His Crohn's Disease Activity Index (CDAI) was 415. Treatment by granulocyte apheresis, mesalazine, and adalimumab was started. His CDAI was 314 on 30 December and 215 on 5 January. A colonoscopic examination on 19 January showed almost complete remission in the transverse colon and marked remission in the rectum. Mesalazine therapy was stopped on 28 February, and the patient was instructed to self-inject 40 mg of adalimumab every other week. His CDAI was 50 on 10 April, indicating clinical remission. His last self-injection of adalimumab was on 24 April 2012, and he started taking 1 g of bovine lactoferrin (bLF) daily. His CDAI was 35 on 8 January 2013. He continued taking 1 g of bLF daily without any other treatment for Crohn's disease. Laboratory blood tests on 7 September 2015 showed no sign of disease recurrence, and a colonoscopic examination on 23 October 2015 showed almost complete mucosal healing. This case indicates that ingestion of bLF to maintain Crohn's disease in a remissive state should be further explored.
Panés, Julián; Rimola, Jordi
Perianal fistulizing Crohn's disease has a major negative effect on patient quality of life and is a predictor of poor long-term outcomes. Factors involved in the pathogenesis of perianal fistulizing Crohn's disease include an increased production of transforming growth factor β, TNF and IL-13 in the inflammatory infiltrate that induce epithelial-to-mesenchymal transition and upregulation of matrix metalloproteinases, leading to tissue remodelling and fistula formation. Care of patients with perianal Crohn's disease requires a multidisciplinary approach. A complete assessment of fistula characteristics is the basis for optimal management and must include the clinical evaluation of fistula openings, endoscopic assessment of the presence of proctitis, and MRI to determine the anatomy of fistula tracts and presence of abscesses. Local injection of mesenchymal stem cells can induce remission in patients not responding to medical therapies, or to avoid the exposure to systemic immunosuppression in patients naive to biologics in the absence of active luminal disease. Surgery is still required in a high proportion of patients and should not be delayed when criteria for drug failure is met. In this Review, we provide an up-to-date overview on the pathogenesis and diagnosis of fistulizing Crohn's disease, as well as therapeutic strategies.
Luján-Sanchis, Marisol; Sanchis-Artero, Laura; Suárez-Callol, Patricia; Medina-Chuliá, Enrique
Capsule endoscopy currently plays a relevant role for Crohn´s disease. This manuscript will discuss the current indications and practical uses of capsule endoscopy in this disease. It is a non-invasive technique that represents a significant advance in the endoscopic diagnosis of small bowel conditions. These circumstances, together with its diagnostic yield and excellent tolerability, make it considerably acceptable by both patients and physicians. This paper discusses the current evidence on the specific circumstances where capsule endoscopy may be indicated for three specific scenarios: Suspected Crohn´s disease, indeterminate colitis, and established Crohn´s disease, where it plays an extensive role. Furthermore, the impact and implications of capsule endoscopy results for follow-up are reviewed. These recommendations must be interpreted and applied in the setting of the integral, individual management of these patients. Understanding its appropriate use in daily clinical practice and an analysis of results may define endoscopic scoring systems to assess activity and mucosal healing in this condition. The present role of capsule endoscopy for Crohn´s disease is subject to ongoing review, and appropriate usage uncovers novel applications likely to result in relevant changes for the future management of these patients.
Deter, Hans-Christian; von Wietersheim, Jörn; Jantschek, Günther; Burgdorf, Friederike; Blum, Brigitta; Keller, Wolfram
Objective Few studies have been published on health care utilization in Crohn's disease and the influence of psychological treatment on high utilizers. Methods The present sub study of a prospective multi center investigation conducted in 87 of 488 consecutive Crohn's disease (CD) patients was designed to investigate the influence of the course of Crohn's disease on health care utilization (hospital days (HD) and sick leave days (SLD) collected by German insurance companies) and to examine the conditions of high-utilizing patients. Predictors of health care utilization should be selected. Based on a standardized somatic treatment, high health care utilizing patients of the psychotherapy and control groups should be compared before and after a one-year treatment. Results Multivariate regression analysis identified disease activity at randomization as an important predictor of the clinical course (r2 = 0.28, p < 0.01). Health care utilization correlated with duration of disease (p < 0.04), but the model was not significant (r2 = 0.15, p = 0.09). The patients' level of anxiety, depression and lack of control at randomization predicted their health-related quality of life at the end of the study (r2 = 0.51, p < 0.00001). Interestingly, steroid intake and depression (t1) predicted the combined outcome measure (clinical course, HRQL, health care utilization) of Crohn's disease at the end of the study (r2 = 0.22, p < 0.001). Among high utilizers, a significantly greater drop in HD (p < 0.03) and in mean in SLD were found in the treatment compared to the control group. Conclusion The course of Crohn's disease is influenced by psychological as well as somatic factors; especially depression seems important here. A significant drop of health care utilization demonstrates the benefit of psychological treatment in the subgroup of high-utilizing CD patients. Further studies are needed to replicate the findings of the clinical outcome in this CD subgroup. PMID:18851749
Golovics, Petra A; Mandel, Michael D; Lovasz, Barbara D; Lakatos, Peter L
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.
Huff, Chad D; Witherspoon, David J; Zhang, Yuhua; Gatenbee, Chandler; Denson, Lee A; Kugathasan, Subra; Hakonarson, Hakon; Whiting, April; Davis, Chadwick T; Wu, Wilfred; Xing, Jinchuan; Watkins, W Scott; Bamshad, Michael J; Bradfield, Jonathan P; Bulayeva, Kazima; Simonson, Tatum S; Jorde, Lynn B; Guthery, Stephen L
Inflammatory bowel disease 5 (IBD5) is a 250 kb haplotype on chromosome 5 that is associated with an increased risk of Crohn's disease in Europeans. The OCTN1 gene is centrally located on IBD5 and encodes a transporter of the antioxidant ergothioneine (ET). The 503F variant of OCTN1 is strongly associated with IBD5 and is a gain-of-function mutation that increases absorption of ET. Although 503F has been implicated as the variant potentially responsible for Crohn's disease susceptibility at IBD5, there is little evidence beyond statistical association to support its role in disease causation. We hypothesize that 503F is a recent adaptation in Europeans that swept to relatively high frequency and that disease association at IBD5 results not from 503F itself, but from one or more nearby hitchhiking variants, in the genes IRF1 or IL5. To test for evidence of recent positive selection on the 503F allele, we employed the iHS statistic, which was significant in the European CEU HapMap population (P=0.0007) and European Human Genome Diversity Panel populations (P≤0.01). To evaluate the hypothesis of disease-variant hitchhiking, we performed haplotype association tests on high-density microarray data in a sample of 1,868 Crohn's disease cases and 5,550 controls. We found that 503F haplotypes with recombination breakpoints between OCTN1 and IRF1 or IL5 were not associated with disease (odds ratio [OR]: 1.05, P=0.21). In contrast, we observed strong disease association for 503F haplotypes with no recombination between these three genes (OR: 1.24, P=2.6×10(-8)), as expected if the sweeping haplotype harbored one or more disease-causing mutations in IRF1 or IL5. To further evaluate these disease-gene candidates, we obtained expression data from lower gastrointestinal biopsies of healthy individuals and Crohn's disease patients. We observed a 72% increase in gene expression of IRF1 among Crohn's disease patients (P=0.0006) and no significant difference in expression of OCTN1
Hernández Jaras, J; García-Samaniego Rey, J; Paraiso Cuevas, V; Castaños-Mollor Penalva, R; Pajares García, J M; Traver Aguilar, J A
A patient with renal colicky pain caused by urinary tract obstruction, as a result of psoas abscess, is presented. It was the first manifestation of Crohn's disease. A Gram negative bacteria was isolated from the abscess. The CT images performed to evaluate the abscess suggested this etiology, even though there were no previous symptoms.
Efsen, Eva; Saermark, Torben; Hansen, Alastair; Bruun, Eywin; Brynskov, Jørn
Increased expression of matrix metalloproteinase (MMP)-2, -3 and -9 has been demonstrated in Crohn's disease fistulas, but it is unknown whether these enzymes are biologically active and represent a therapeutic target. Therefore, we investigated the proteolytic activity of MMPs in fistula tissue and examined the effect of inhibitors, including clinically available drugs that beside their main action also suppress MMPs. Fistula specimens were obtained by surgical excision from 22 patients with Crohn's disease and from 10 patients with fistulas resulting from other causes. Colonic endoscopic biopsies from six controls were also included. Total functional MMP activity was measured by a high-pressure liquid chromatography (HPLC)-based, fluorogenic MMP-substrate cleavage assay, and the specific activity of MMP-2, -3 and -9 by the MMP Biotrak Activity Assay. The MMP inhibitors comprised ethylene-diamine-tetraacetic acid (EDTA), the synthetic broad-spectrum inhibitor, GM6001, the angiotensin-converting enzyme (ACE) inhibitor, ramiprilate, and the tetracycline, doxycycline. In Crohn's disease fistulas, about 50% of the total protease activity was attributable to MMP activity. The average total MMP activity was significantly higher (about 3.5-times) in Crohn's fistulas (471 FU/μg protein, range 49-2661) compared with non-Crohn's fistulas [134 FU/μg protein, range 0-495, (p < 0.05)] and normal colon [153 FU/μg protein, range 77-243, (p < 0.01)]. MMP-3 activity was increased in Crohn's fistulas (1.4 ng/ml, range 0-9.83) compared with non-Crohn's fistulas, [0.32 ng/ml, range 0-2.66, (p < 0.02)]. The same applied to MMP-9 activity [0.64 ng/ml, range 0-5.66 and 0.17 ng/ml, range 0-1.1, respectively (p < 0.04)]. Ramiprilate significantly decreased the average total MMP activity level by 42% and suppressed the specific MMP-3 activity by 72%, which is comparable to the effect of GM6001 (87%). Moreover, MMP-9 activity was completely blunted by ramiprilate. Doxycycline had no
Mansuri, Ishrat; Fletcher, Joel G; Bruining, David H; Kolbe, Amy B; Fidler, Jeff L; Samuel, Sunil; Tung, Jeanne
Pediatric small-bowel (SB) Crohn disease (CD) may be missed if the terminal ileum (TI) appears normal at endoscopy and SB imaging is not performed. We sought to estimate the prevalence and clinical characteristics of pediatric patients with CD and endoscopic skipping of the TI-that is, pediatric patients with active SB or upper gut inflammation and an endoscopically normal TI. This retrospective study included pediatric patients with CD who underwent both CT enterography (CTE) or MR enterography (MRE) and ileocolonoscopy within a 30-day period between July 2004 and April 2014. The physician global assessment was used as the reference standard for SB CD activity. Radiologists reviewed the CTE and MRE studies for inflammatory parameters; severity, length, and multifocality of SB inflammation; and the presence of penetrating complications. Of 170 patients who underwent ileal intubation, the TI was macroscopically normal or showed nonspecific inflammation in 73 patients (43%). Nearly half (36/73, 49%) of the patients with normal or nonspecific findings at ileocolonoscopy had radiologically active disease with a median length of SB involvement of 20 cm (range, 1 to > 100 cm). Seventeen (47%) of these patients had multifocal SB involvement and five (14%) had penetrating complications. Overall, endoscopic TI skipping was present in 43 (59%) patients with normal or nonspecific ileocolonoscopic findings: 20 with histologic inflammation (17 with positive imaging findings), 14 with inflammation at imaging only, and nine with proximal disease (upper gut, jejunum, or proximal ileum). There were no significant differences in the clinical parameters of the patients with and those without endoscopic TI skipping. Ileocolonoscopy may miss SB CD in pediatric patients that is due to isolated histologic, intramural, or proximal inflammation. Enterography is complementary to ileocolonoscopy in the evaluation of pediatric CD.
Amitai, Michal M; Raviv-Zilka, Lisa; Hertz, Marjorie; Erlich, Zippora; Konen, Eli; Ben-Horin, Shomron; Apter, Sara
Only a few studies have compared the accuracy of magnetic resonance enterography (MRE) and computed tomography enterography (CTE) in the diagnosis of Crohn's disease and its complications. To compare the sensitivity of MRE and CTE analysis in their ability to detect, sign-by-sign, 10 classical imaging signs of Crohn's disease. The study group comprised 42 biopsy-proven Crohn's disease patients who underwent both CTE and MRE within an average period of 6 weeks. Agreement between the two modalities in detecting the 10 most significant radiological signs of CD was evaluated using the Kappa index. The sensitivity of MRE and CTE was calculated using a standard of reference composed of all the findings seen by CTE and/or MRE. We analyzed MRE and CTE sensitivity separately in two groups, according to the time interval between the examinations. Agreement between CTE and MRE was more than 70% in 8 of the 10 signs: mural thickening, phlegmon, stenosis, skip lesions, mucosal stratification, fistula, abscess, and creeping fat. The Kappa level of agreement values for CTE versus MRE varied between substantial for phlegmon and skip lesions; moderate for fistula, creeping fat, abscess and mural thickening; and fair for stenosis and dilatation. CTE detected more findings than MRE, except for creeping fat and fistula. There was no significant difference in the sensitivity of CTE and MRE in the two groups defined by the time interval (time < 1.5 and time > 1.5 months) except for detection of dilatation. Almost all imaging signs of Crohn's disease were detected equally well by both modalities regardless of the time interval between examinations. We therefore consider MRE to be reliable for imaging and follow-up in patients with Crohn's disease who may need recurrent imaging.
Sciarretta, G; Furno, A; Mazzoni, M; Basile, C; Malaguti, P
Scintigraphy with autologous granulocytes labelled by technetium-99m hexamethyl, propylene amine oxime (99mTc-HMPAO) was performed in 103 Crohn's disease patients and 52 healthy controls. In 31 patients endoscopic and histologic activity was compared with scan activity index. In the 98 patients with a positive scan, the extent of Crohn's disease, assessed by scintigraphy, was compared with that evaluated by small bowel x ray or colonoscopy with biopsies. In 48 patients, Crohn's disease activity index, activity index, simple index, erythrocyte sedimentation rate, C-reactive protein were correlated with the scan results. In 16 patients the five parameters and scan were repeated after treatment with methyl-prednisolone (10 cases), enteral nutrition (3), and 5-acetylsalicylic acid (3). The results showed that 99mTc-HMPAO granulocyte scan had a 95% sensitivity and 100% specificity to detect active inflammation; it correctly showed an abscess or a fistula in all the 24 cases found. The correlation between histological inflammatory activity and scan activity index was highly significant (r = 0.85; p < 0.01), less significant (r = 0.65; p < 0.01) between endoscopy and scan activity index. The evaluation for the extent of Crohn's disease by scan was completely correct in the small bowel (100%) and 93% correct in the large bowel. No correlation was seen between the three clinical activity parameters and scanning; in more than 80% of the cases in remission on the basis of a clinical or laboratory index, scintigraphy remained positive. Medical treatment was effective on the clinical indices but not on the active inflammation in the ileum, whereas it led to a negative scan in 5/11 cases in the large intestine. Scintigraphy with 99mTc-HMPAO granulocyte plays an important part in Crohn's disease for the diagnosis of complications, for activity and assessment of the extent, and for the treatment results evaluation. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:8244102
Krupnick, A S; Morris, J B
Crohn's disease is a panenteric, transmural inflammatory disease of unknown origin. Although primarily managed medically, 70% to 90% of patients will require surgical intervention. Surgery for small bowel Crohn's is usually necessary for unrelenting stenotic complications of the disease. Fistula, abscess, and perforation can also necessitate surgical intervention. Most patients benefit from resection or strictureplasty with an improved quality of life and remission of disease, but recurrence is common and 33% to 82% of patients will need a second operation, and 22% to 33% will require more than two resections. Short-bowel syndrome is unavoidable in a small percentage of Crohn's patients because of recurrent resection of affected small bowel and inflammatory destruction of the remaining mucosa. Although previously a lethal and unrelenting disease with death caused by malnutrition, patients with short-bowel syndrome today can lead productive lives with maintenance on total parenteral nutrition (TPN). This lifestyle, however, does not come without a price. Severe TPN-related complications, such as sepsis of indwelling central venous catheters and liver failure, do occur. Future developments will focus on more powerful and effective anti-inflammatory medication specifically targeting the immune mechanisms responsible for Crohn's disease. Successful medical management of the disease will alleviate the need for surgical resection and reduce the frequency of short-bowel syndrome. Improving the efficacy of immunosuppression and the understanding of tolerance induction should increase the safety and applicability of small-bowel transplant for those with short gut. Tissue engineering offers the potential to avoid immunosuppression altogether and supplement intestinal length using the patient's own tissues.
Wilkens, Rune; Novak, Kerri L; Lebeuf-Taylor, Eleonore; Wilson, Stephanie R
Background and Aims. We aim to evaluate the benefit of ultrasound in the assessment of Crohn's disease and to demonstrate its potential contribution to disease management. Methods. We conduct a retrospective review of adult patients with Crohn's disease examined with sonography and colonoscopy within 30 days. Study patients were identified in whom colonoscopy did not access a pathological segment, detected and evaluated by ultrasonography. Changes in management were predominantly attributed to ultrasound in those cases where the diseased segment was not assessed on endoscopy. Results. From 115 patients with temporally related ileocolonoscopy and ultrasound, 41 had disease fully assessed on ultrasound only, with complications in 26/41. Twenty-nine of 41 had mild or no endoscopic inflammation with moderate or severe disease on ultrasound at the same segment or at a segment proximal to the reach of the endoscope. Changes in management were significantly attributed to ultrasound in 22 of these 29 patients. Conclusion. The benefit of cross-sectional imaging is invaluable for the comprehensive assessment of bowel not shown on ileocolonoscopy. Ultrasound may make a significant contribution to correct classification of disease extent and severity of Crohn's disease. Prospective studies are needed to further understand the contribution of US in patient management.
Novak, Kerri L.; Lebeuf-Taylor, Eleonore; Wilson, Stephanie R.
Background and Aims. We aim to evaluate the benefit of ultrasound in the assessment of Crohn's disease and to demonstrate its potential contribution to disease management. Methods. We conduct a retrospective review of adult patients with Crohn's disease examined with sonography and colonoscopy within 30 days. Study patients were identified in whom colonoscopy did not access a pathological segment, detected and evaluated by ultrasonography. Changes in management were predominantly attributed to ultrasound in those cases where the diseased segment was not assessed on endoscopy. Results. From 115 patients with temporally related ileocolonoscopy and ultrasound, 41 had disease fully assessed on ultrasound only, with complications in 26/41. Twenty-nine of 41 had mild or no endoscopic inflammation with moderate or severe disease on ultrasound at the same segment or at a segment proximal to the reach of the endoscope. Changes in management were significantly attributed to ultrasound in 22 of these 29 patients. Conclusion. The benefit of cross-sectional imaging is invaluable for the comprehensive assessment of bowel not shown on ileocolonoscopy. Ultrasound may make a significant contribution to correct classification of disease extent and severity of Crohn's disease. Prospective studies are needed to further understand the contribution of US in patient management. PMID:27446873
Bhatnagar, Gauraang; Von Stempel, Conrad; Halligan, Steve; Taylor, Stuart A
Cross sectional Imaging plays an increasingly important role the diagnosis and management of Crohn's disease. Particular emphasis is placed on MRI and Ultrasound as they do not impart ionising radiation. Both modalities have reported high sensitivity for disease detection, activity assessment and evaluation of extra-luminal complications, and have positive effects on clinical decision making. International Guidelines now recommend MRI and Ultrasound in the routine management of Crohn's disease patients. This article reviews the current evidence base supporting both modalities with an emphasis on the key clinical questions. We describe current protocols, basic imaging findings and highlight areas in need of further research. 5 Technical Efficacy: Stage 4 J. MAGN. RESON. IMAGING 2017;45:1573-1588. © 2016 International Society for Magnetic Resonance in Medicine.
Park, Hyun C; Kim, Hyun W; Park, Chan G; Ko, Joo Y
Cutaneous manifestations are well-recognized complications of Crohn disease (CD) that can be divided into disease-specific and reactive conditions. One of the most common reactive conditions is erythema nodosum (EN), which presents as subcutaneous tender nodules most often on the legs. On the other hand, metastatic Crohn disease (MCD) is a rare cutaneous manifestation of CD defined as the presence of noncaseating granulomas that are not contiguous with the gastrointestinal (GI) tract. The clinical presentation of MCD is variable; however, lesions often are located on the legs and genital region. We report the case of a 21-year-old woman with a 6-year history of CD who presented with MCD clinically simulating EN.
Nickerson, T. Paul; Merchea, Amit
The management of inflammatory bowel disease (IBD) is medically and surgically complex. Numerous patient- and disease-oriented factors must be considered in treating patients with IBD, including nutritional replenishment/support, effect of immunosuppressive medications, extent of resection, and use of proximal diversion. Perioperative planning and optimization of the patient is imperative to ensuring favorable outcomes and limiting morbidity. These perioperative considerations in Crohn disease and ulcerative colitis are reviewed here. PMID:27247531
Hansen, Lars F; Jakobsen, Christian; Paerregaard, Anders; Qvist, Niels; Wewer, Vibeke
The aim of this study was to describe surgery rates, complications, and risk of disease recurrence after surgery in paediatric Crohn disease (CD). Children <18 years with a diagnosis of CD and a least 1 intestinal resection from the period January 1, 1978 to December 31, 2007 were identified using the Danish National Patient Registry. Patient charts were used to extract data. A total of 115 of 422 children with CD, who had surgery in 2 referral centres, were further studied. Disease extension according to the Montreal classification at the time of operation was available in 106/115 patients: B1, 39/106 (37%); B2, 59/106 (56%); and B3, 8/106 (7%). Before/after surgery 89%/36% of the patients received corticosteroids, 26%/61% azathioprine, and 15%/34% infliximab. Ileocoecal resection was performed in 54 (47%); 17 (15%) underwent ileal resection, 21 (18%) colectomy, 13 (11%) hemicolectomy, and 10 (9%) a combined colonic and ileal resection. Median time from diagnosis to surgery was 23 months (range 0-147). The median follow-up time after surgery was 121 months (16-226), and median time to disease recurrence was 12 months (3-160). The cumulative clinical recurrence rates at 1, 5, and 10 years were 50%, 73%, and 77%, respectively. More than 1 bowel resection was needed in 39%. Postoperative azathioprine treatment did not affect rate of recurrence after surgery. In this large cohort of children with CD studied for >10 years postoperatively, we found a high postoperative recurrence rate of disease and a frequent need for >1 intestinal resection.
Cooper, Jason G; Purcell, Gretchen P
Crohn's disease is a debilitating condition that affects the entire gastrointestinal tract and often requires aggressive and invasive therapies. Several studies have suggested dietary triggers for disease activity. We have created a web-based tool to allow participants to record both daily food intake and wellness (i.e., disease-specific quality of life). We seek to determine if measurable correlations exist between these events in patients with Crohn's disease. Advanced data mining techniques are employed to find such correlations and the efficacies of chosen techniques are assessed. We tested our web-based system in a pilot study involving 7 participants, and we found that traditional statistical techniques identified diet and disease activity correlations in short-term data sets.
Zou, L; Adegun, O K; Willis, A; Fortune, Farida
Crohn's disease is a chronic relapsing and remitting inflammatory condition which affects any part of the gastrointestinal tract. In the oro-facial region, patients can present peri-oral swellings which results in severe facial disfigurement. To date, assessing the degree of facial changes and evaluation of treatment outcomes relies on clinical observation and semi-quantitative methods. In this paper, we describe the development of a robust and reproducible measurement strategy using 3-D facial biometrics to objectively quantify the extent and progression of oro-facial Crohn's disease. Using facial laser scanning, 32 serial images from 13 Crohn's patients attending the Oral Medicine clinic were acquired during relapse, remission, and post-treatment phases. Utilising theories of coordinate metrology, the facial images were subjected to registration, regions of interest identification, and reproducible repositioning prior to obtaining volume measurements. To quantify the changes in tissue volume, scan images from consecutive appointments were compared to the baseline (first scan image). Reproducibility test was performed to ascertain the degree of uncertainty in volume measurements. 3-D facial biometric imaging is a reliable method to identify and quantify peri-oral swelling in Crohn's patients. Comparison of facial scan images at different phases of the disease revealed precisely profile and volume changes. The volume measurements were highly reproducible as adjudged from the 1% standard deviation. 3-D facial biometrics measurements in Crohn's patients with oro-facial involvement offers a quick, robust, economical and objective approach for guided therapeutic intervention and routine assessment of treatment efficacy on the clinic.
Kia, Richard; White, David; Sarkar, Sanchoy
Whilst ascites is a common presenting complaint in patients with decompensated chronic liver disease and disseminated malignancy, in Crohn's disease however, it is exceptionally rare. We describe a patient with no prior history of inflammatory bowel or liver disease, presenting with rapid onset gross ascites and scrotal swelling. Further investigations revealed severe hypoalbuminemia and transudative ascitic fluid with normal other liver function tests and a negative liver screen. Computed tomography revealed widespread ascites and pleural effusions with no features of malignancy or portal hypertension, and a small bowel barium series showed features of fistulating small bowel Crohn's disease. An ileo-colonoscopy confirmed the presence of terminal ileal inflammatory stricture. The patient's clinical condition and serum albumin improved with a combination of diuretics, elemental diet, antibiotics and oral 5-aminosalicylic acid therapy.
DiLauro, Steven; Crum-Cianflone, Nancy F.
Ileitis, or inflammation of the ileum, is often caused by Crohn’s disease. However, ileitis may be caused by a wide variety of other diseases. These include infectious diseases, spondyloarthropathies, vasculitides, ischemia, neoplasms, medication-induced, eosinophilic enteritis, and others. The clinical presentation of ileitis may vary from an acute and self-limited form of right lower quadrant pain and/or diarrhea, as in the majority of cases of bacterial ileitis, but some conditions (ie, vasculitis or Mycobacterium tuberculosis) follow a chronic and debilitating course complicated by obstructive symptoms, hemorrhage, and/or extraintestinal manifestations. Ileitis associated with spondylarthropathy or nonsteroidal anti-inflammatory drugs is typically subclinical and often escapes detection unless further testing is warranted by symptoms. In a minority of patients with long-standing Crohn’s ileitis, the recrudescence of symptoms may represent a neoplasm involving the ileum. Distinguishing between the various forms of ileitis remains a test of clinical acumen. The diagnosis of the specific etiology is suggested by a detailed history and physical examination, laboratory testing, and ileocolonoscopy and/or radiologic data. PMID:20532706
Saint-Raymond, A; Arnaud-Battandier, F; Schmitz, J
Enteral nutrition in children with Crohn's disease is a preferred treatment of acute attacks. When maintained for three months, it effectively acts on digestive symptoms, makes possible the resumption of growth and onset of a delayed puberty. In contrast, it does not appear to modify the long-term course of the disease: 7 out of 10 patients had relapses 3 to 6 months after interruption of enteral nutrition.
D'Incà, Renata; Caccaro, Roberta
Maintenance of medically induced remission is a clinical challenge in Crohn's disease (CD), since it is a chronic disease and that often occurs in young people. The introduction of immunosuppressors and biologics has significantly improved the management of these patients, however efficacy and safety of these treatments in the very long term still needs clarification. Furthermore, scientific research is driven more into new drugs to induce remission rather then maintenance.
Botros, Youssef; Mathews, Mary; Patel, Hiren; Shah, Nihar; Baddoura, Walid; de la Torre, Andrew
Hepatocellular carcinoma (HCC) usually occurs in patients with underlying risk factors such as liver cirrhosis and chronic hepatitis B. Although patients with Crohn's disease (CD) are at an increased risk to develop malignancies such as colon cancer, the incidence of HCC in this population is extremely rare. We report a case of 62-year-old male with long history of CD treated with azathioprine (AZA) and aminosalicylic acid (ASA) who was incidentally diagnosed with HCC, for which left hepatectomy was done. Four years later during routine follow-up, patient had another hepatic lesion and underwent resection of the mass. The mechanism of occurrence of HCC in patient with CD is still controversial and may include immune mediated changes and medication related complications. AZA was reported in all case reports of CD that developed HCC. Through this report we hope to explore the complex pathophysiological mechanisms contributing to the development of HCC in the Crohn's disease patient population. PMID:26788381
Aguilera, V; Calvo, F; Nos, P; Molla, A; Esteban, R; Ponce, J
Presacral abscess is a rare musculoskeletal complication of Crohn's disease. The clinical picture is sometimes insidious and a delay in diagnosis may increase morbidity. Abdominal-pelvic computerized axial tomography (CAT) has proven to be very useful in the diagnosis of this entity, which usually requires surgical treatment. We present the case of a 22-year-old man who presented to hospital for colic-type abdominal pain of 6 months' evolution and intermittent episodes of joint pain. The patient also presented mechanical pain in the right gluteus muscle of two weeks' evolution irradiating to the posterior side of the muscle. Complementary investigations confirmed the suspected diagnosis of Crohn's disease and showed presacral abscess. Treatment was surgical.
Iborra, Marisa; Moret, Inés; Rausell, Francisco; Bastida, Guillermo; Aguas, Mariam; Cerrillo, Elena; Nos, Pilar; Beltrán, Belén
There is increasing interest in oxidative stress being a potential aetiological factor and/or a triggering factor in Crohn's disease, rather than a concomitant occurrence during the pathogenesis of the disease. Recent research has shown that the immune mononuclear cells of Crohn's disease patients are induced to produce hydrogen peroxide (H2O2). Similarly, the regulation of antioxidant enzymes during disease in these cells has been unravelled, showing that SOD (superoxide dismutase) activity and GPx (glutathione peroxidase) activity is increased during active disease and returns to normal in remission phases. However, catalase remains constantly inhibited which supports the idea that catalase is not a redox-sensitive enzyme, but a regulator of cellular processes. ROS (reactive oxygen species) can be produced under the stimulus of different cytokines such as TNFα (tumour necrosis factor α). It has been shown in different experimental models that they are also able to regulate apoptosis and other cellular processes. The status of oxidative stress elements in Crohn's disease and their possible implications in regulating cellular processes are reviewed in the present paper.
Quintana, C.; Galleguillos, L.; Benavides, E.; Quintana, J. C.; Zúñiga, A.; Duarte, I.; Klaassen, J.; Kolbach, M.; Soto, R. M.; Iacobelli, S.; Álvarez, M.; O'Brien, A.
Determining the diagnosis of Crohn's disease has been highly difficult mainly during the first years of this study carried out at the Pontificia Universidad Catolica (PUC) Clinical Hospital. For instance, it has been frequently confused with Irritable bowel syndrome and sometimes misdiagnosed as ulcerative colitis, infectious colitis or enterocolitis, intestinal lymphoma, or coeliac disease. Consequently, it seems advisable to characterize what the most relevant clinical features are, in order to establish a clear concept of Crohn's disease. This difficulty may still be a problem at other medical centers in developing countries. Thus, sharing this information may contribute to a better understanding of this disease. Based on the clinical experience gained between 1963 and 2004 and reported herein, the main clinical characteristics of the disease are long-lasting day and night abdominal pain, which becomes more intense after eating and diarrhoea, sometimes associated to a mass in the abdomen, anal lesions, and other additional digestive and nondigestive clinical features. Nevertheless, the main aim of this work has been the following: is it possible to make, in an early stage, the diagnosis of Crohn's disease with a high degree of certainty exclusively with clinical data? PMID:23213555
Shenoy-Bhangle, Anuradha; Nimkin, Katherine; Goldner, Dana; Bradley, William F; Israel, Esther J; Gee, Michael S
Magnetic resonance imaging (MRI) is considered the imaging standard for diagnosis and characterization of perianal complications associated with Crohn disease in children and adults. To define MRI criteria that could act as potential predictors of treatment response in fistulizing Crohn disease in children, in order to guide more informed study interpretation. We performed a retrospective database query to identify all children and young adults with Crohn disease who underwent serial MRI studies for assessment of perianal symptoms between 2003 and 2010. We examined imaging features of perianal disease including fistula number, type and length, presence and size of associated abscess, and disease response/progression on follow-up MRI. We reviewed imaging studies and electronic medical records. Statistical analysis, including logistic regression, was performed to associate MR imaging features with treatment response and disease progression. We included 36 patients (22 male, 14 female; age range 8-21 years). Of these, 32 had a second MRI exam and 4 had clinical evidence of complete response, obviating the need for repeat imaging. Of the parameters analyzed, presence of abscess, type of fistula according to the Parks classification, and multiplicity were not predictors of treatment outcome. Maximum length of the dominant fistula and aggregate fistula length in the case of multiple fistulae were the best predictors of treatment outcome. Maximum fistula length <2.5 cm was a predictor of treatment response, while aggregate fistula length ≥2.5 cm was a predictor of disease progression. Perianal fistula length is an important imaging feature to assess on MRI of fistulizing Crohn disease.
Hohwieler, M; Renz, S; Liebau, S; Lin, Q; Lechel, A; Klaus, J; Perkhofer, L; Zenke, M; Seufferlein, T; Illing, A; Müller, M; Kleger, A
Human pluripotent stem cells represent a powerful tool to study human embryonic development and disease but also open up novel strategies for cell replacement therapies. Their capacity to give rise to every cell type of the human body, meanwhile, enables researchers to generate high yields of mesodermal, ectodermal, but also endodermal-derived tissues such as hepatic, pancreatic, or intestinal cells. Another progress in the field came with the advent of 3-dimensional culture conditions, so-called organoids, which facilitate maturation of stem cells and in turn more faithfully recapitulate human tissue architecture. While several studies reported the derivation of organoid cultures from adult intestinal tissue, the derivation of intestinal organoids derived from plucked human hair of Crohn's disease patients has not been reported. The current research project reports such successful generation and characterization of induced pluripotent stem cells (iPSCs) derived from hair sheet keratinocyte cultures of a patient with Crohn's disease. Stepwise differentiation along the intestinal lineage showed no differences in intermediate stages such as definitive endoderm formation. We also directed the patterned primitive gut tube toward intestinal organoids resembling the cellular architecture of human "miniguts". As expected from current pathophysiological knowledge on Crohn's disease, there were no obvious morphological differences in the "miniguts" derived from healthy control and diseased patient-induced pluripotent stem cells. Taken together, our platform will enable for detailed and complementary phenotyping of the pathophysiology of Crohn's disease in a novel disease-in-a-dish format. © Georg Thieme Verlag KG Stuttgart · New York.
Ganesan, Srinivasan; Travis, Simon P L; Ahmad, Tariq; Jazrawi, Riadh
Therapeutic options for patients with refractory ulcerative colitis or Crohn's disease have recently been augmented by the introduction of biological therapies. The pro-inflammatory cytokine, tumor necrosis factor (TNF)-alpha is present in elevated concentrations in patients with inflammatory bowel disease and inhibitors of TNF alpha have proved effective as treatment. Strategies aimed at reducing TNF in patients with Crohn's disease, include the mouse/human chimeric monoclonal antibody, infliximab (Centocor Inc), the humanized monoclonal antibody, CDP-571 (Celltech Group plc), the human recombinant TNF receptor fusion protein, etanercept (Immunex Corp), and thalidomide. New approaches, including the use of soluble TNF receptors, appear promising. This article reviews the evidence of therapeutic inhibition of TNF.
The alterations in the gut microbiota observed in patients with inflammatory bowel disease and in particular in Crohn's disease and in ulcerative colitis patients with pouchitis, provide the rationale for administering probiotic agents in the medical treatment of those conditions. In the maintenance treatment of inactive Crohn's disease probiotics, when administered alone, were found ineffective in preventing clinical and/or endoscopic recurrence. By contrast, a combination of a probiotic agent (eg, Saccharomyces boulardii) with standard pharmacological therapy can promote clinical benefit. In patients with pouchitis, so far only the probiotic mixture VSL #3 proved to effectively prevent relapses after successful antibiotic treatment of active inflammation. Further controlled studies, enrolling higher numbers of patients, are needed to better identify the exact role of probiotics in this area.
Hrnčířová, Lucia; Krejsek, Jan; Šplíchal, Igor; Hrnčíř, Tomáš
Crohn's disease is a chronic immune-mediated intestinal inflammation targeted against a yet incompletely defined subset of commensal gut microbiota and occurs on the background of a genetic predisposition under the influence of environmental factors. Genome-wide association studies have identified about 70 genetic risk loci associated with Crohn's disease. The greatest risk for Crohn's disease represent polymorphisms affecting the CARD15 gene encoding nucleotide-binding oligomerization domain 2 (NOD2) which is an intracellular sensor for muramyl dipeptide, a peptidoglycan constituent of bacterial cell wall. The accumulated evidence suggests that gut microbiota represent an essential, perhaps a central factor in the induction and maintaining of Crohn's disease where dysregulation of normal co-evolved homeostatic relationships between intestinal microbiota and host mucosal immune system leads to intestinal inflammation. Taken together, these findings identify Crohn's disease as a syndrome of overlapping phenotypes that involves variable influences of genetic and environmental factors. A deeper understanding of different genetic abnormalities underlying Crohn's disease together with the identification of beneficial and harmful components of gut microbiota and their interactions are essential conditions for the categorization of Crohn's disease patients, which enable us to design more effective, preferably causative, individually tailored therapy.
Sons, H U; Dannberg, A; Jerosch, J; Dellmann, A
Articular changes in Chron's disease represent extraintestinal organic manifestations which generally take the form of so-called enteropathic synovitis. Articular alterations - diagnosed as non-specific arthritis in the great majority of cases--may precede the intestinal disease. In very rare cases it can be shown that the joints display histological changes typical of Morbus Crohn. The etiology and pathophysiological mechanisms of the articular changes are not clear. Probable factors are: autoimmune disease, stimulation of the immunological system by exogenous antigens, induction of a self-sustaining inflammatory process, and demonstrable circulation of antigen-antibody complexes. Genetic factors seem to play a role (familial disposition). A pure "colonic Crohn" (= colitis granulomatosa) leads to a higher degree of articular alteration than a pure "small-intestine Crohn" (= ileitis terminalis). The joints preferentially affected are in the region of the lower extremities (knee and ankle joints). Concomitant Bekhterev's disease (spondylitiis ankylopoietica) is found in 7-10% of cases. Osteomyelitis represents a rare and serious complication: it can appear in the course of chronic Chron's disease (mainly with intestinal fistulas), especially in the region of the pelvic bones. Further aspects of interest from an orthopedic viewpoint are hypertrophic osteoarthropathy with periossal neoformation, granulomatous changes in the bone itself, and aseptic osteonecrosis.
Piton, Nicolas; Roquet, Marie-Laurence; Sibert, Louis; Sabourin, Jean-Christophe
Crohn's disease is a systemic disease and sometimes involves the testicle, usually leading to granulomatous lesions. We report herein a case of focal non-granulomatous orchitis in a 21-year-old patient with active Crohn's disease treated by an anti-tumor necrosis factor monoclonal antibody. This circumscribed testicular lesion mimicked a tumor, leading to orchiectomy. Pre-operative blood tests (i.e. alpha-fetoprotein, lactate dehydrogenase and human chorionic gonadotrophin) were strictly normal Pathological examination of the testicle revealed a focal inflammatory infiltrate predominantly composed of lymphocytes accompanied by few plasma cells, lacking giant cells or granulomas. Importantly, intratubular germ cell neoplasia, atrophy or lithiasis were not observed.After discussing and excluding other plausible causes (burnt-out /regressed germ cell tumor, infection, vascular or traumatic lesions, iatrogenic effects), we concluded that this particular case of orchitis was most likely an extra-digestive manifestation of inflammatory bowel disease. To our knowledge, this is the first described case of focal non-granulomatous orchitis associated with Crohn's disease. Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2117747284160112.
Matsueda, K; Shoda, R; Takazoe, M; Hiwatashi, N; Bamba, T; Kobayashi, K; Saito, T; Terano, A; Yao, T
Crohn's disease (CD) often flares up and requires frequent hospitalization and/or surgery. Cyclic home elemental enteral alimentation (C-HEEA) was developed to prevent flare-up of CD and to minimize patient hospitalization. However, its therapeutic efficacy has not been studied in a large patient population. Therefore, questionnaires were sent to members of the Inflammatory Bowel Disease (IBD) Research Group of Japan to evaluate the therapeutic efficacy of C-HEEA and to define the factors that may affect the efficacy of the treatment. Data for 410 patients (C-HEEA-treated n = 322; drug-treated n = 88) were collected from 29 institutions and analysis showed the following results. The cumulative remission and non-hospitalization rates of the C-HEEA treated group were significantly higher than the rates of the drug-treated group in all patients and in those with ileitis and ileo-colitis (P < 0.0001, P < 0.001, and P < 0.01, respectively), but no significant difference was noted in patients with colitis. Cumulative remission and non-hospitalization rates were also influenced by the daily calorie content of the elemental diet (ED); more than 1200 kcal of the ED per day was found to be more effective than lower amounts to maintain remission and to prevent hospitalization. The therapeutic efficacy of C-HEEA was shown to be superior to that of drug treatment in patients with CD with ileal involvement, and it is suggested that more than 1200kcal per day should be supplied by the ED to enhance its therapeutic efficacy.
Akobeng, Anthony K; Elawad, Mamoun; Gordon, Morris
Crohn's disease is a chronic relapsing condition of the alimentary tract with a high morbidity secondary to bowel inflammation. Glutamine plays a key role in maintaining the integrity of the intestinal mucosa and has been shown to reduce inflammation and disease activity in experimental models of Crohn's disease. To evaluate the efficacy and safety of glutamine supplementation for induction of remission in Crohn's disease. We searched the following databases from inception to November 15, 2015: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane IBD Group Specialised Register. Study references were also searched for additional trials. There were no language restrictions. Randomised controlled trials (RCTs) that compared glutamine supplementation administered by any route to a placebo, active comparator or no intervention in people with active Crohn's disease were considered for inclusion. Two authors independently extracted data and assessed the methodological quality of the included studies. The Cochrane risk of bias tool was used to assess methodological quality. The primary outcome measure was clinical or endoscopic remission. Secondary outcomes included intestinal permeability, clinical response, quality of life, growth in children and adverse events. Risk ratios and 95% confidence intervals were calculated for dichotomous outcomes. The overall quality of the evidence supporting the primary outcome was evaluated using the GRADE criteria. Two small RCTs (total 42 patients) met the inclusion criteria and were included in the review. One study (18 patients) compared four weeks of treatment with a glutamine-enriched polymeric diet (42% amino acid composition) to a standard polymeric diet (4% amino acid composition) with low glutamine content in paediatric patients (< 18 years of age) with active Crohn's disease. The other study (24 patients) compared glutamine-supplemented total parenteral nutrition to non-supplemented total
Smith, Jill P; Stock, Heather; Bingaman, Sandra; Mauger, David; Rogosnitzky, Moshe; Zagon, Ian S
Endogenous opioids and opioid antagonists have been shown to play a role in healing and repair of tissues. In an open-labeled pilot prospective trial, the safety and efficacy of low-dose naltrexone (LDN), an opioid antagonist, were tested in patients with active Crohn's disease. Eligible subjects with histologically and endoscopically confirmed active Crohn's disease activity index (CDAI) score of 220-450 were enrolled in a study using 4.5 mg naltrexone/day. Infliximab was not allowed for a minimum of 8 wk prior to study initiation. Other therapy for Crohn's disease that was at a stable dose for 4 wk prior to enrollment was continued at the same doses. Patients completed the inflammatory bowel disease questionnaire (IBDQ) and the short-form (SF-36) quality of life surveys and CDAI scores were assessed pretreatment, every 4 wk on therapy and 4 wk after completion of the study drug. Drug was administered by mouth each evening for a 12-wk period. Seventeen patients with a mean CDAI score of 356 +/- 27 were enrolled. CDAI scores decreased significantly (P= 0.01) with LDN, and remained lower than baseline 4 wk after completing therapy. Eighty-nine percent of patients exhibited a response to therapy and 67% achieved a remission (P < 0.001). Improvement was recorded in both quality of life surveys with LDN compared with baseline. No laboratory abnormalities were noted. The most common side effect was sleep disturbances, occurring in seven patients. LDN therapy appears effective and safe in subjects with active Crohn's disease. Further studies are needed to explore the use of this compound.
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Hodges, P; Gee, M; Grace, M; Sherbaniuk, R W; Wensel, R H; Thomson, A B
A detailed nutrient assessment was made of 23 male and 24 female patients with Crohn's disease who entered sequentially into an outpatient clinic. Assessment included 48-hour dietary recall, anthropometric measurements, and biochemical and hematological tests appropriate to characterize protein-energy malnutrition. Approximately 40% of patients had energy intakes equal to only two-thirds of the Recommended Dietary Allowance (RDA). Three men and five women had relative body weights less than 85% of standard, but body weight was not correlated with energy intake. Relative body weight was correlated with arm muscle circumference in both male and female patients and with triceps skinfold and total lymphocyte count in women. Although the mean protein intake was greater than 150% of the RDA, evidence of protein malnutrition included low arm muscle circumference in 14% of the men and 15% of the women, low serum albumin concentration in 13% of the women, and low total lymphocyte count in one-half of the patients. The Crohn's disease activity index was correlated significantly with serum albumin, energy intake, and duration of disease in men and with serum ferritin and hemoglobin concentration in women. Thus, a reduced relative body weight or reduced serum albumin was not uncommon in patients with Crohn's disease but did not necessarily occur in those with reduced intakes of protein and energy. However, a low relative body weight may indicate need for further nutritional assessment.
Clark, Jeffrey G; Srinath, Arvind I; Youk, Ada O; Kirshner, Margaret A; McCarthy, F Nicole; Keljo, David J; Bousvaros, Athos; DeMaso, David R; Szigethy, Eva M
The aim of the study was to determine whether infliximab use and other potential predictors are associated with decreased prevalence and severity of depression in pediatric patients with Crohn disease (CD). A total of 550 (n = 550) youth ages 9 to 17 years with biopsy-confirmed CD were consecutively recruited as part of a multicenter randomized controlled trial. Out of the 550, 499 patients met study criteria and were included in the analysis. At recruitment, each subject and a parent completed the Children's Depression Inventory (CDI). A child or parent CDI score ≥ 12 was used to denote clinically significant depressive symptoms (CSDS). Child and parent CDI scores were summed to form total CDI (CDIT). Infliximab use, demographic information, steroid use, laboratory values, and Pediatric Crohn's Disease Activity Index (PCDAI) were collected as the potential predictors of depression. Univariate regression models were constructed to determine the relations among predictors, CSDS, and CDIT. Stepwise multivariate regression models were constructed to predict the relation between infliximab use and depression while controlling for other predictors of depression. Infliximab use was not associated with a decreased proportion of CSDS and CDIT after adjusting for multiple comparisons. CSDS and CDIT were positively associated with PCDAI, erythrocyte sedimentation rate, and steroid dose (P < 0.01) and negatively associated with socioeconomic status (SES) (P < 0.001). In multivariate models, PCDAI and SES were the strongest predictors of depression. Disease activity and SES are significant predictors of depression in youth with Crohn disease.
Neufeld, David; Keidar, Andrei; Gutman, Mordechai; Zissin, Rivka
Abdominal wall abscess due to Crohn's Disease used to be one of the definitive indications for operative treatment. The advent of interventional radiology, the accessibility to percutaneous drainage, and the availability of new medications raised the possibility of nonoperative treatment of this condition. The clinical presentation, treatment, and follow-up of 13 patients with abdominal wall abscesses secondary to Crohn's Disease were retrospectively reviewed. During a 10-year period (1993-2003), 13 patients with abdominal wall abscess were treated. Five patients had an anterolateral abdominal wall abscess and eight had a posterior abscess (psoas). In 11 patients, 17 drainage procedures were performed: 12 percutaneous and 5 operative. Despite initial adequate drainage and resolution of the abscess, all 13 patients eventually needed resection of the offending bowel segment, which was undertaken in 12 patients. The mean time between abscess presentation and definitive operation was 2 months. Percutaneous drainage is an attractive option in most cases of abdominal abscesses. However, in Crohn's Disease patients with an abdominal wall abscess, we found a high failure rate despite initial adequate drainage. We suggest that surgical resection of the diseased bowel segment should be the definitive therapy.
Jigaranu, Anca Olivia; Nedelciuc, Otilia; Blaj, Andreea; Badea, Mircea; Mihai, Catalina; Diculescu, Mircea; Cijevschi-Prelipcean, Cristina
Recent studies indicate that persistent intestinal inflammation in patients with Crohn's disease (CD) might be caused by abnormal intestinal microbiota. This hypothesis may suggest a beneficial effect of antibiotics in CD therapy. So far, guidelines do not recommend antibiotics except in the treatment of complicated CD, and there are few studies on the effects of rifaximin in these patients. Between December 2011 and December 2012, we performed a blinded randomized trial in 168 patients with a previous history of moderately active CD concerning the efficacy of rifaximin. All the patients had previously achieved remission with standard therapy (prednisone/budesonide). Data from patients receiving 800 mg of rifaximin (83 patients) twice a day for 12 weeks were compared with those from patients who received placebo (83 patients). The primary endpoint was maintaining remission during the follow-up. All the patients (100%; 83/83) on 800 mg of rifaximin were in remission after 12 weeks of treatment in comparison with 84% (70/83) of the placebo group. This significant difference was also persistent at the 24-week follow-up [78% (65/83) vs. 41% (34/83), respectively]. The last evaluation performed at 48 weeks revealed disease activity in 45% (38/83) of the patients of the rifaximin group, i.e. a significant decrease compared with the placebo group [75% (63 of 83)]. Remission previously obtained with standard treatment can be sustained in patients with moderately active CD after the administration of 800 mg of rifaximin. © 2014 S. Karger AG, Basel.
Goldberg, H.I.; Gore, R.M.; Margulis, A.R.; Moss, A.A.; Baker, E.L.
The abdominal and pelvic computed tomographic examinations in 28 patients with Crohn disease were analyzed and correlated with conventional barium studies, sinograms, and surgical findings. Mucosal abnormalities such as aphthous lesions, pseudopolyps, and ulcerations were only imaged by conventional techniques. Computed tomography proved superior in demonstrating the mural, serosal, and mesenteric abnormalities such as bowel wall thickening (82%), fibrofatty proliferation of mesenteric fat (39%), mesenteric abscess (25%), inflammatory reaction of the mesentery (14%), and mesenteric lymphadenopathy (18%). Computed tomography was most useful clinically in defining the nature of mass effects, separation, or displacement of small bowel segments seen on small bowel series. Although conventional barium studies remain the initial diagnostic procedure in evaluating Crohn disease, computed tomography can be a useful adjunct in resolving difficult clinical and radiologic diagnostic problems.
To, N; Gracie, D J; Ford, A C
Tobacco smoking is a well-established risk factor for the development of Crohn's disease, and this may lead to a more complicated disease course. However, recent evidence suggests that many patients with Crohn's disease are unaware of this fact. To perform a systematic review and meta-analysis of the effects of smoking on disease course in Crohn's disease. A search of MEDLINE, EMBASE and EMBASE classic was carried out (up to July 2015) to identify observational studies reporting data on smoking and rates of surgery or flares of disease activity in patients with Crohn's disease. Dichotomous data were pooled to obtain odds ratios (ORs) for flares of disease activity or need for surgery, with 95% confidence intervals (CIs). The search identified 33 eligible studies. Compared with nonsmokers, smokers had increased odds of flare of disease activity (OR, 1.56; 95% CI, 1.21-2.01), flare after surgery (OR, 1.97; 95% CI, 1.36-2.85), need for first surgery (OR, 1.68; 95% CI, 1.33-2.12) and need for second surgery (OR, 2.17; 95% CI, 1.63-2.89). The odds of these outcomes among ex-smokers diminished upon smoking cessation, with ORs comparable to those among nonsmokers and, in the case of flare or second surgery, significantly lower than smokers. Smokers with Crohn's disease have a more complicated disease course than nonsmokers, and quitting smoking may ameliorate this. Patients should be reminded of the detrimental effects of smoking on the course of their disease, and smoking cessation advice should be provided to reduce disease burden and costs in these patients. © 2016 John Wiley & Sons Ltd.
Gans, M; Taylor, C
A 51-year-old man who had undergone several partial bowel resections for Crohn's disease presented with progressively decreased night vision. Electroretinography showed a flat scotopic response and a diminished, delayed photopic response. Measurement of stool fat showed marked fat malabsorption. Treatment with parenteral nutrition, including administration of vitamin A, resulted in marked improvement in the scotopic and photopic response and subjective improvement in his night vision. Patients with malabsorption states should be followed to avoid irreversible visual loss.
Majoor, C; Schreurs, A; Weers-Pothoff, G
A 48 year old patient with active Crohn's disease presented with bilateral nodules over his lungs resembling malignant metastasis. Bronchoscopic and pathological examination of the airways and sputum did not show any malignancy. After 6 weeks Mycobacterium xenopi was cultured from his bronchial washings while all other cultures remained negative. Treatment was started with rifampicin, ethambutol, and clarithromycin and, after 9 months of treatment, there was an almost complete resolution of his chest radiograph. PMID:15223876
Shaoul, Ron; Rimar, Yosi; Toubi, Aurora; Mogilner, Jorge; Polak, Reuven; Jaffe, Michael
The clinical diagnosis of classic Crohn's disease (CD) of the small bowel is based on a typical history, tender right lower quadrant fullness or mass, and characteristic radiographic findings of the terminal ileum. Appendicitis may as well present with chronic or recurrent symptoms and this presentation may be confused with CD. We herein describe the case of a young teenage girl with a presumptive diagnosis of CD, who was ultimately diagnosed as having chronic nongranulomatous appendicitis. The literature on the subject is reviewed.
Fiasse, R; Lurhuma, A Z; Cambiaso, C L; Masson, P L; Dive, C
Circulating immune complexes were determined in 59 consecutive patients with Crohn's disease and 100 blood donors by a double method based on the inhibition of the agglutinating activity of CIq and/or rheumatoid factor on the IgG-coated polystyrene particles. In patients, the incidence of positive immune complexes was 63% and 61% at first testing, 85% and 78% at subsequent determinations; there was a good correlation between the inhibition titres of CIq and those of rheumatoid factor (p less than 0.001). In blood donors, the incidence was 22% and 14% at low titre. The incidence of immune complexes was the lowest (36%) in the group of resected patients without signs of relapse; repeat determinations showed absence of immune complexes three months postoperatively. In patients medically treated for primary disease or relapse, rheumatoid factor titre higher than 1/1 was less frequent than in medically untreated patients with active disease (p less than 0.01). A significantly higher concentration of serum alpha-1-antitrypsin and orosomucoid, and a significantly lower level of serum iron were found in patients with an IC titre exceeding 1/1; longitudinal studies showed in most cases a concordance between the evolution of immune complex titres, inflammatory parameters and clinical status. PMID:308030
Zaman, Taufiq; Watson, Joseph; Zaman, Mohammad
Crohn disease is an immune-mediated inflammatory condition with gastrointestinal and extraintestinal manifestations in patients. Pulmonary involvement of Crohn disease is one manifestation. There have been case reports which have shown Crohn disease and lung nodules which were noted to be histopathological as cryptogenic organizing pneumonia (COP). In our case, a 22-year-old woman with Crohn disease was seen with complaints of chest pain and cough. Computed tomographic scan of chest showed multiple bilateral lung nodules, for which biopsy was done, which showed COP. The case study is followed by a deeper discussion of COP and the extraintestinal manifestation seen in inflammatory bowel disease. PMID:28579861
Zaman, Taufiq; Watson, Joseph; Zaman, Mohammad
Crohn disease is an immune-mediated inflammatory condition with gastrointestinal and extraintestinal manifestations in patients. Pulmonary involvement of Crohn disease is one manifestation. There have been case reports which have shown Crohn disease and lung nodules which were noted to be histopathological as cryptogenic organizing pneumonia (COP). In our case, a 22-year-old woman with Crohn disease was seen with complaints of chest pain and cough. Computed tomographic scan of chest showed multiple bilateral lung nodules, for which biopsy was done, which showed COP. The case study is followed by a deeper discussion of COP and the extraintestinal manifestation seen in inflammatory bowel disease.
Kuriyama, M; Kato, J; Morimoto, N; Fujimoto, T; Okada, H; Yamamoto, K
Crohn's disease patients often carry gastroduodenal lesions. However, few reports have addressed specific gastroduodenoscopic findings in Crohn's disease patients. The gastroduodenoscopic findings of 63 Crohn's disease patients were examined. Those of 62 ulcerative colitis and 63 age- and gender-matched gastroesophageal reflux disease patients were also reviewed as controls. Findings of bamboo-joint-like appearance, gastric antral erosions, and duodenal lesions were the specific findings that were highlighted. Of 63 Crohn's disease patients, 47 (75%) had at least one of the specific gastroduodenoscopic findings, and the prevalence of these findings was significantly higher in Crohn's disease patients than in ulcerative colitis and gastroesophageal reflux disease patients (ulcerative colitis, 24/62, 39%; gastroesophageal reflux disease, 15/63, 24%, P < 0.0001). In particular, bamboo-joint-like appearance was almost unique to Crohn's disease patients (Crohn's disease, 28/63, 44%; ulcerative colitis, 3/62, 5%; gastroesophageal reflux disease, 0/63, 0%, P < 0.0001). Analysis of the relationship between the Crohn's disease patient's background and gastrodunodenoscopic findings revealed that both patients with disease affecting the ileum and those with previous gut operations were more likely to exhibit the specific gastroduodenoscopic findings (P = 0.030 and P = 0.043, respectively). Specific gastroduodenoscopic findings were observed in Crohn's disease patients. In particular, bamboo-joint-like appearance could be a unique marker of Crohn's disease.
Arvanitis, Marina; DeWalt, Darren A; Martin, Christopher F; Long, Millie D; Chen, Wenli; Jaeger, Beth; Sandler, Robert S; Kappelman, Michael D
To assess the criterion validity and responsiveness of Patient-Reported Outcomes Measurement Information System (PROMIS) in a web-based cohort of children with Crohn's disease. We recruited children with Crohn's disease (ages 9-17 years) and their parents from the web-based Crohn's and Colitis Foundation of America Kids and Teens Study cohort. Upon entry into the cohort and 6 months later, children self-reported Crohn's disease activity, health-related quality of life, and PROMIS domains of pain interference, anxiety, depression, fatigue, and peer relationships. Mean PROMIS scores for the 276 participating patients were worse among those with worse self-reported Crohn's disease activity (per Short Crohn's Disease Activity Index, P < .005 for all), Crohn's disease activity in the prior 6 months (per Manitoba Index, P < .01 for all), and health-related quality of life (per IMPACT-35, P < .001 for all). One hundred forty-three patients and their parents completed follow-up questionnaires, 75% of whom reported stable disease activity. Those with improved Crohn's disease activity reported improved PROMIS scores, and those with worsened Crohn's disease activity reported worse PROMIS scores for all domains except anxiety. All participants reported improved anxiety from baseline, but those with stable or worsened Crohn's disease activity reported less improvement (P = .07). PROMIS scores were significantly associated with Crohn's disease activity in a linear and clinically meaningful manner, and responded to change in Crohn's disease activity over a 6-month period. This supports the criterion validity and responsiveness of pediatric PROMIS. Copyright © 2016 Elsevier Inc. All rights reserved.
Foster, Erina N.; Nguyen, Khanh K.; Sheikh, Rafiq A.; Prindiville, Thomas P.
The association of Crohn's disease (CD) and Sweet's syndrome is rare and the presence of Sjögren's syndrome in Crohn's disease is even rarer, with only three reports found in the literature. We describe two cases of Crohn's disease associated with Sweet's syndrome, one of which is the first case of CD and Sweet's concomitantly associated with Sjögren's syndrome. Both cases responded rapidly to Infliximab therapy with complete resolution of the skin lesions. PMID:16050146
Park, Seong Ho
The purpose of this article is to provide a comprehensive review regarding DWI enterography used for evaluating Crohn disease and to summarize the relevant evidence. Active bowel inflammation in Crohn disease causes restricted diffusion on MR enterography with DWI. Enterographic DWI to evaluate Crohn disease is increasingly drawing attention for both academic research and clinical practice and has shown potential as a quantitative tool for assessing bowel inflammation. DWI enterography also has multiple unresolved issues and limitations.
Freeman, H J
An international working party at the World Congress of Gastroenterology held in Vienna, Austria from September 6 to 11, 1998 defined a classification for Crohn's disease based on patient age at diagnosis (eg, less than 40 years of age, 40 years of age or older), disease location (eg, terminal ileum, colon, ileocolon or upper gastrointestinal tract) and behaviour (eg, stricturing, penetrating). Disease location in the upper gastrointestinal tract was defined by disease being present proximal to the terminal ileum, regardless of terminal ileal or colon involvement. A 20-year, single clinician database of 877 patients from a university campus hospital was used, and comprised 492 women (56.1%) and 385 men (43.9%). Of these patients, 740 (84.4%) were diagnosed before age 40 years and 137 (15.6%) were diagnosed by 40 years of age or older. Disease was located in the terminal ileum alone in 222 patients (25.3%), colon alone in 238 patients (27.2%) and ileocolon in 304 patients (34.6%). Another 113 patients (13.1%) had disease in the upper gastrointestinal tract, usually with disease also in the terminal ileum (23 patients), colon (12 patients) or ileocolon (71 patients). Only seven of 877 patients had disease located in the upper gastrointestinal tract alone with no distal disease. Disease behaviour could be classified as nonstricturing and nonpenetrating in 256 patients (29.2%), stricturing in 294 patients (33.6%) and penetrating in 327 patients (37.2%). Of the 877 patients with Crohn's disease, 837 were white, 38 were Asian and two were black. In this tertiary care setting of a single clinician practice in a Canadian teaching hospital at the University of British Columbia, Crohn's disease predominantly affects women, and young adults with a high rate of stricturing and penetrating complications.
Pugmire, Brian S; Gee, Michael S; Kaplan, Jess L; Hahn, Peter F; Doody, Daniel P; Winter, Harland S; Gervais, Debra A
Intra-abdominal abscess is a common complication of Crohn disease in children. Prior studies, primarily in adults, have shown that percutaneous abscess drainage is a safe and effective treatment for this condition; however, the data regarding this procedure and indications in pediatric patients is limited. Our aim was to determine the success rate of percutaneous abscess drainage for abscesses related to Crohn disease in pediatric patients with a focus on treatment endpoints that are relevant in the era of biological medical therapy. We retrospectively reviewed 25 cases of patients ages ≤20 years with Crohn disease who underwent percutaneous abscess drainage. Technical success was defined as catheter placement within the abscess with reduction in abscess size on post-treatment imaging. Clinical success was defined as (1) no surgery within 1 year of drainage or (2) surgical resection following drainage with no residual abscess at surgery or on preoperative imaging. Multiple clinical parameters were analyzed for association with treatment success or failure. All cases were classified as technical successes. Nineteen cases were classified as clinical successes (76%), including 7 patients (28%) who required no surgery within 1 year of percutaneous drainage and 12 patients (48%) who had elective bowel resection within 1 year. There was a statistically significant association between resumption of immunosuppressive therapy within 8 weeks of drainage and both clinical success (P < 0.01) and avoidance of surgery after 1 year (P < 0.01). Percutaneous abscess drainage is an effective treatment for Crohn disease-related abscesses in pediatric patients. Early resumption of immunosuppressive therapy is statistically associated with both clinical success and avoidance of bowel resection, suggesting a role for percutaneous drainage in facilitating prompt initiation of medical therapy and preventing surgical bowel resection.
Steiner, Steven J; Noe, Joshua D; Denne, Scott C
Children with Crohn disease have altered growth and body composition. Previous studies have demonstrated decreased protein breakdown after either corticosteroid or anti-TNF-α therapy. The aim of this study was to evaluate whole body protein metabolism during corticosteroid therapy in children with newly diagnosed Crohn disease. Children with suspected Crohn disease and children with abdominal symptoms not consistent with Crohn disease underwent outpatient metabolic assessment. Patients diagnosed with Crohn disease and prescribed corticosteroid therapy returned in 2 wk for repeat metabolic assessment. Using the stable isotopes [d5] phenylalanine, [1-(13)C] leucine, and [(15)N(2)] urea, protein kinetics were determined in the fasting state. Thirty-one children (18 controls and 13 newly diagnosed with Crohn disease) completed the study. There were no significant differences in protein breakdown or loss between patients with Crohn disease at diagnosis and controls. After corticosteroid therapy in patients with Crohn disease, the rates of appearance of phenylalanine (32%) and leucine (26%) increased significantly, reflecting increased protein breakdown, and the rate of appearance of urea also increased significantly (273%), reflecting increased protein loss. Whole body protein breakdown and loss increased significantly after 2 wk of corticosteroid therapy in children with newly diagnosed Crohn disease, which may have profound effects on body composition.
El-Tawil, A M
In Great Britain, married couples were reported to have between 1.9 and 2.1 children, while men with Crohn's disease had a mean of 1.2 and of 0.4 children before and after diagnosis, respectively. The role of zinc for male fertility is essential. Although lack of zinc in Crohn's disease is well established in up to 70% of patients, a possible relation between zinc deficiency and male subfertility in Crohn's disease remains unclear. This study is aimed at examining a possible link between zinc deficiency in men with Crohn's disease and male subfertility in this group of patients.
de la Fuente-Fernández, R.; Rubio-Nazabal, E.; de la Iglesia-Martínez, F.
A variety of extraintestinal manifestations, probably immune-mediated, may appear during relapses of Crohn's disease. We report the clinical observation of a 34-year-old woman who developed a Guillain-Barré syndrome, aphthous stomatitis and oligoarthritis during a relapse of Crohn's ileocolitis. This case suggests that the Guillain-Barré syndrome may be another extraintestinal manifestation of Crohn's disease. PMID:7567741
D'Incà, Renata; Caccaro, Roberta
Crohn's disease (CD) is a chronic inflammatory bowel disease characterized by a relapsing-remitting clinical behavior and dominated by intestinal inflammation. Being a chronic disorder that with time develops into a disabling disease, it is important to monitor the severity of inflammation to assess the efficacy of medication, rule out complications, and prevent progression. This is particularly true now that the goals of treatment are mucosal healing and deep remission. Endoscopy has always been the gold standard for assessing mucosal activity in CD, but its use is limited by its invasiveness and its inability to examine the small intestine, proximal to the terminal ileum. Enteroscopy and the less invasive small bowel capsule endoscopy enable the small bowel to be thoroughly explored and scores are emerging for classifying small bowel disease activity. Cross-sectional imaging techniques (ultrasound, magnetic resonance, computed tomography) are emerging as valid tools for monitoring CD patients, assessing inflammatory activity in the mucosa and the transmucosal extent of the disease, and for excluding extra-intestinal complications. Neither endoscopy nor imaging are suitable for assessing patients frequently, however. Noninvasive markers such as C-reactive protein, and fecal biomarkers such as calprotectin and lactoferrin, are therefore useful to confirm the inflammatory burden of the disease and to identify patients requiring further investigations.
Ben Salem, Chaker; Salem, Chaker B; Larif, Sofiene; Fathallah, Neila; Slim, Raoudha; Aounallah, Amina; Sakhri, Jaballah; Hmouda, Houssem
Sweet's syndrome has been reported in association with inflammatory diseases such as Crohn's disease. It has also been reported in association with several drugs. Here, we report a rare case of Sweet's syndrome induced by azathioprine in a patient with Crohn's disease.
Ibrahim, Toni; El Karak, Fady; Araji, Assem; El Rassy, Elie
A 69-year-old man, with severe refractory Crohn's disease, presented with acute coronary syndrome that required angioplasty. He developed severe tirofiban-induced thrombocytopenia (TIT) heralded by type I allergic reaction that required steroids and a combination of antihistamine H1 and antihistamine H2 for symptomatic management. The thrombocytopenia spontaneously resolved uneventfully in 48 hours thereafter. This case report suggests a possible association between TIT and inflammatory bowel disease. Therefore, strict monitoring of the platelet count is required in patients who develop allergic reactions to tirofiban. PMID:27144035
Kristo, Ivan; Stift, Anton; Bergmann, Michael; Riss, Stefan
Crohn's disease (CD) still remains a challenging chronic inflammatory disorder, both for colorectal surgeons and gastroenterologists. The need for recurrent surgery following primary intestinal resection is still considerable, though recent evidence suggested a declining rate of recurrence. Several conflicting surgical parameters have been identified that might impact on the postoperative outcome positively, such as access to the abdomen, anastomotic configuration or type of disease. Additionally, promising results have been achieved with the increased use of immunosuppressive medications in CD. Consequently, the question arises if we are getting better as a result of novel medical and surgical strategies.
Aniwan, Satimai; Park, Sang Hyoung; Loftus, Edward V
Crohn's disease (CD) is a chronic condition that can result in significant morbidity and disability. By studying the association between demographics and initial clinical features and subsequent natural history, one may be able to stratify patients by their risks of clinical relapse, hospitalization, and surgery. Understanding the potential environmental risk factors and natural history of CD in a given patient guides the physician when counseling the patient and selecting a treatment strategy. In this review, updated data regarding the incidence and prevalence of CD, important environmental risk factors, natural history of the disease, and important prognostic factors are discussed. Copyright © 2017 Elsevier Inc. All rights reserved.
Schicho, Rudolf; Storr, Martin
In ancient medicine, cannabis has been widely used to cure disturbances and inflammation of the bowel. A recent clinical study now shows that the medicinal plant Cannabis sativa has lived up to expectations and proved to be highly efficient in cases of inflammatory bowel diseases. In a prospective placebo-controlled study, it has been shown what has been largely anticipated from anecdotal reports, i.e. that cannabis produces significant clinical benefits in patients with Crohn's disease. The mechanisms involved are not yet clear but most likely include peripheral actions on cannabinoid receptors 1 and 2, and may also include central actions. © 2013 S. Karger AG, Basel.
Nunes, T; Etchevers, M J; Domènech, E; García-Sánchez, V; Ber, Y; Peñalva, M; Merino, O; Nos, P; Garcia-Planella, E; Casbas, A G; Esteve, M; Taxonera Samsó, C; Montoro Huguet, M; Gisbert, J P; Martín Arranz, M D; García-Sepulcre, M F; Barreiro-de Acosta, M; Beltrán, B; Alcaide Suárez, N; Saro Gismera, C; Cabriada, J L; Cañas-Ventura, A; Gomollón, F; Panés, J
Recently, the notion that smoking may adversely affect Crohn's disease (CD) outcomes has been challenged by the suggestion that the widespread use of immunosuppressants and anti-TNF drugs might offset the adverse effects of tobacco. To reassess the influence of tobacco smoking on disease phenotype and complications on a time-dependent analysis, taking into account the different therapeutic interventions. We designed a retrospective cohort study of 3224 patients with Crohn's disease. The data were collected from the Spanish national inflammatory bowel disease registry (ENEIDA), including information regarding demographics, clinical characteristics, disease complications, therapeutic interventions and smoking status. Patients were classified as nonsmokers, smokers and former smokers, according to their present and past smoking habits. In the univariate analysis, smokers had more strictures (22.6% vs. 19.3%, P < 0.05) and less colonic involvement (7.2% vs. 10.9%, P < 0.05), and were more frequently under treatment with steroids (91.6% vs. 85.8%, P < 0.05), immunosuppressants (73.5% vs. 63.6% P < 0.05) or anti-TNF drugs (31.4% vs. 25.1%, P < 0.05) than nonsmokers. In the time-dependent multivariate analysis, smokers were found to have a significantly decreased survival free of stricturing disease (HR: 1.5, CI 95% 1.18-1.90) or perianal complications (HR: 1.50, CI 95% 1.01-1.46), and had a higher risk for requiring thiopurine therapy (HR: 1.20, CI 95% 1.05-1.30). These results suggest that, despite the widespread use of immunosuppressants and anti-TNF drugs, smokers with Crohn's disease still have a more severe disease course, with increased therapeutic requirements when compared with nonsmokers. © 2013 John Wiley & Sons Ltd.
Imaging of the small bowel is complicated by its length and its overlapping loops. Recently, however, the development of crosssectional imaging techniques, such as computed tomography enterography (CTE) and magnetic resonance enterography (MRE) has shifted fundamental paradigms in the diagnosis and management of patients with suspected or known Crohn's disease (CD). CTE and MRE are noninvasive imaging tests that involve the use of intraluminal oral and intravenous contrast agents to evaluate the small bowel. Here, we review recent advances in each cross-sectional imaging modality, their advantages and disadvantages, and their diagnostic performances in the evaluation of small bowel lesions in CD. PMID:25691841
Stewart, Kristen M A
This article discusses the clinical evaluation and approach to patients with 3 complex ulcerative vulvar conditions: hidradenitis suppurativa, metastatic Crohn disease of the vulva, and aphthous ulcers. These conditions are particularly challenging to medical providers because, although each is known to present with nonspecific examination findings that vary in morphology, the predominance of the diagnosis is based on clinical examination and exclusion of a wide variety of other conditions. Care of patients with these conditions is further complicated by the lack of therapeutic data and the significant impact these conditions have on quality of life. Copyright © 2017 Elsevier Inc. All rights reserved.
Sandborn, William J; Feagan, Brian G; Rutgeerts, Paul; Hanauer, Stephen; Colombel, Jean-Frédéric; Sands, Bruce E; Lukas, Milan; Fedorak, Richard N; Lee, Scott; Bressler, Brian; Fox, Irving; Rosario, Maria; Sankoh, Serap; Xu, Jing; Stephens, Kristin; Milch, Catherine; Parikh, Asit
The efficacy of vedolizumab, an α4β7 integrin antibody, in Crohn's disease is unknown. In an integrated study with separate induction and maintenance trials, we assessed intravenous vedolizumab therapy (300 mg) in adults with active Crohn's disease. In the induction trial, 368 patients were randomly assigned to receive vedolizumab or placebo at weeks 0 and 2 (cohort 1), and 747 patients received open-label vedolizumab at weeks 0 and 2 (cohort 2); disease status was assessed at week 6. In the maintenance trial, 461 patients who had had a response to vedolizumab were randomly assigned to receive placebo or vedolizumab every 8 or 4 weeks until week 52. At week 6, a total of 14.5% of the patients in cohort 1 who received vedolizumab and 6.8% who received placebo were in clinical remission (i.e., had a score on the Crohn's Disease Activity Index [CDAI] of ≤150, with scores ranging from 0 to approximately 600 and higher scores indicating greater disease activity) (P=0.02); a total of 31.4% and 25.7% of the patients, respectively, had a CDAI-100 response (≥100-point decrease in the CDAI score) (P=0.23). Among patients in cohorts 1 and 2 who had a response to induction therapy, 39.0% and 36.4% of those assigned to vedolizumab every 8 weeks and every 4 weeks, respectively, were in clinical remission at week 52, as compared with 21.6% assigned to placebo (P<0.001 and P=0.004 for the two vedolizumab groups, respectively, vs. placebo). Antibodies against vedolizumab developed in 4.0% of the patients. Nasopharyngitis occurred more frequently, and headache and abdominal pain less frequently, in patients receiving vedolizumab than in patients receiving placebo. Vedolizumab, as compared with placebo, was associated with a higher rate of serious adverse events (24.4% vs. 15.3%), infections (44.1% vs. 40.2%), and serious infections (5.5% vs. 3.0%). Vedolizumab-treated patients with active Crohn's disease were more likely than patients receiving placebo to have a remission, but
Kaakoush, Nadeem O.; Day, Andrew S.; Huinao, Karina D.; Leach, Steven T.; Lemberg, Daniel A.; Dowd, Scot E.
Microbial dysbiosis has been suggested to be involved in the pathogenesis of Crohn's disease (CD); however, many studies of gut microbial communities have been confounded by environmental and patient-related factors. In this study, the microbial flora of fecal samples from 19 children newly diagnosed with CD and 21 age-matched controls were analyzed using high-throughput sequencing to determine differences in the microbial composition between CD patients and controls. Analysis of the microbial composition of specific bacterial groups revealed that Firmicutes percentages were significantly lower in CD patients than in controls and that this was due largely to changes in the class Clostridia. Bacteroidetes and Proteobacteria percentages were higher and significantly higher in CD patients than in controls, respectively. Both the detection frequencies of Bacteroidetes and Firmicutes correlated (positively and negatively, respectively) with the calculated pediatric Crohn's disease activity index scores of patients. Upon further analysis, differences in the microbial compositions of patients with mild disease and moderate to severe disease were identified. Our findings indicate that a combination of different bacterial species or a dynamic interplay between individual species is important for disease and is consistent with the dysbiosis hypothesis of CD. PMID:22837318
Segal, Dan; Macdonald, John K; Chande, Nilesh
Crohn's disease is a transmural, relapsing inflammatory condition afflicting the digestive tract. Opioid signalling, long known to affect secretion and motility in the gut, has been implicated in the inflammatory cascade of Crohn's disease. Low dose naltrexone, an opioid antagonist, has garnered interest as a potential therapy. The primary objective was to evaluate the efficacy and safety of low dose naltrexone for induction of remission in Crohn's disease. A systematic search of MEDLINE, EMBASE, CENTRAL, and the Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Review Group Specialized Register was performed from inception to February 2013 to identify relevant studies. Abstracts from major gastroenterology conferences including Digestive Disease Week and United European Gastroenterology Week and reference lists from retrieved articles were also reviewed. Randomized controlled trials of low dose naltrexone (LDN) for treatment of active Crohn's disease were included. Data were analyzed on an intention-to-treat basis using Review Manager (RevMan 5.2). The primary outcome was induction of clinical remission defined by a Crohn's disease activity index (CDAI) of < 150 or a pediatric Crohn's disease activity index (PCDAI) of < 10. Secondary outcomes included clinical response (70- or 100-point decrease in CDAI from baseline), endoscopic remission or response, quality of life, and adverse events as defined by the included studies. Risk ratios (RR) and 95% confidence intervals (CI) were calculated for dichotomous outcomes. The methodological quality of included studies was evaluated using the Cochrane risk of bias tool. The overall quality of the evidence supporting the primary outcome and selected secondary outcomes was assessed using the GRADE criteria. Two studies were identified (46 participants). One study assessed the efficacy and safety of 12 weeks of LDN (4.5 mg/day) treatment compared to placebo in adult patients (N = 34). The other study assessed
Bourreille, Arnaud; Cadiot, Guillaume; Le Dreau, Gérard; Laharie, David; Beaugerie, Laurent; Dupas, Jean-Louis; Marteau, Philippe; Rampal, Patrick; Moyse, Dominique; Saleh, Ashraf; Le Guern, Marie-Emmanuelle; Galmiche, Jean-Paul
Saccharomyces boulardii is a probiotic yeast that has been shown to have beneficial effects on the intestinal epithelial barrier and digestive immune system. There is preliminary evidence that S boulardii could be used to treat patients with Crohn's disease (CD). We performed a randomized, placebo-controlled trial to evaluate the effects of S boulardii in patients with CD who underwent remission during therapy with steroids or aminosalicylates. We performed a prospective study of 165 patients who achieved remission after treatment with steroids or salicylates; they were randomly assigned to groups given S boulardii (1 g/day) or placebo for 52 weeks. The primary end point was the percentage of patients in remission at week 52. Time to relapse, Crohn's disease activity index scores, and changes in parameters of inflammation were secondary end points. CD relapsed in 80 patients, 38 in the S boulardii group (47.5%) and 42 in the placebo group (53.2%, a nonsignificant difference). The median time to relapse did not differ significantly between patients given S boulardii (40.7 weeks) vs placebo (39.0 weeks). There were no significant differences between groups in mean Crohn's disease activity index scores or erythrocyte sedimentation rates or in median levels of C-reactive protein. In a post hoc analysis, nonsmokers given S boulardii were less likely to experience a relapse of CD than nonsmokers given placebo, but this finding requires confirmation. Although the probiotic yeast S boulardii is safe and well tolerated, it does not appear to have any beneficial effects for patients with CD in remission after steroid or salicylate therapies. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.
Vasiliauskas, E; Kam, L; Karp, L; Gaiennie, J; Yang, H; Targan, S
BACKGROUND—Perinuclear antineutrophil cytoplasmic antibodies (pANCA) have been detected in a clinically distinct Crohn's disease subpopulation. Antibodies to Saccharomyces cerevisiae (ASCA) have been demonstrated in the majority of patients with Crohn's disease. AIMS—To examine the relationship between selective marker antibody expression in Crohn's disease and disease onset, location, and clinical behaviour patterns. METHODS—Sera from 156 consecutive patients with established Crohn's disease were evaluated in a blinded fashion for the presence of ASCA and ANCA. Clinical profiles were generated by investigators blinded to immune marker status. RESULTS—Using multiple regression analyses, higher ASCA levels were shown to be independently associated with early age of disease onset as well as both fibrostenosing and internal penetrating disease behaviours. Higher ANCA levels were associated with later age of onset and ulcerative colitis-like behaviour. Substratification of the Crohn's disease population using selective ANCA and ASCA expression (high levels of a single marker antibody): (1) distinguished homogeneous subgroups that manifested similar disease location and behaviours; and (2) identified patients with more aggressive small bowel disease. CONCLUSIONS—The findings suggest that by taking into account the magnitude of the host immune response, Crohn's disease can now be stratified on an immunological basis into more homogeneous clinically distinct subgroups, characterised by greater uniformity among anatomical distribution of disease and disease behaviour. Keywords: antineutrophil cytoplasmic antibody; anti-Saccharomyces cerevisiae antibody; Crohn's disease; inflammatory bowel disease; ulcerative colitis PMID:10986208
Bonse-Geuking, Ulrich; Kraus, Michael
A 64 year old male patient suffering from Crohn's disease received infliximab therapy for a period of 5 months prior to presentation to our hospital. Due to the symptoms fever, ascites, and diffuse abdominal tenderness on palpation of unknown origin, a CT scan of the abdomen was performed and led to the suspected diagnosis of a peritoneal carcinomatosis. QuantiFERON™ test revealed a tuberculosis infection and molecular analyses of a peritoneal specimen obtained by laparoscopy clearly identified Mycobacterium tuberculosis DNA. Quadruple tuberculostatic therapy was initiated and the patient's condition continuously improved thereafter.
Fluxá, Daniela; Kronberg, Udo; Lubascher, Jaime; O'Brien, Andrés; Las Heras, Facundo; Ibáñez, Patricio; Quera, Rodrigo
Benign multicystic peritoneal mesothelioma is an uncommon lesion arising from the peritoneal mesothelium. It is asymptomatic or presents with unspecific symptoms. Imaging techniques may reveal it, however the final diagnosis can only be made by histopathology. Surgery is the only effective treatment considering its high recurrence rate. We report a 19 years old male with Crohns disease. Due to persistent abdominal pain, an abdominal magnetic resonance imaging was performed, showing a complex cystic mass in the lower abdomen. The patient underwent surgery and the lesion was completely resected. The pathological study reported a benign multicystic peritoneal mesothelioma.
Golpe, Rafael; Mateos, Alfonso; Pérez-Valcárcel, Javier; Lapeña, José A; García-Figueiras, Roberto; Blanco, Joaquín
Crohn's disease (CD) can be associated with respiratory involvement. Multiple pulmonary nodules are an infrequent finding in patients with CD. When they are found, histology usually shows sterile necrobiotic nodules, which are spherical aggregates of neutrophils, which frequently cavitate. We report a patient with inactive CD treated with mesalazine, who presented with multiple pulmonary nodules. Transthoracic biopsy of one of the nodules disclosed a benign, nongranulomatous inflammatory lymphoid infiltration. The radiographic abnormalities responded well to oral prednisone. Focal, nongranulomatous lymphoid infiltration thus must be considered in the differential diagnosis of multiple pulmonary nodules in patients with CD.
Hu, Huiqin; Wang, Xinying; Liu, Side
Abstract Background: Thalidomide has been successful use in patients with refractory Crohn disease (CD) in recent years. Methods: We collected the data of a postoperative CD patient who was prescribed thalidomide to induce remission and reviewed the relevant literatures. Results: A 51-year-old female was diagnosed as CD after an urgent terminal intestinal resection and presented endoscopic recurrence despite the prophylactic treatment with azathioprine (AZA). Fortunately, she achieved mucosal healing (MH) at a low dose of thalidomide for 15 months. Conclusion: Thalidomide is effective to induce MH in the postoperative CD endoscopic recurrence. PMID:27603389
Yacyshyn, B R; Pilarski, L M
Crohn's disease is an immunoregulatory disorder of the intestine that can be associated with systemic manifestations. This study analysed B-cell differentiation antigens to identify B-cell subpopulations unique to patients with Crohn's disease. CD45 isoform expression was used as an indicator of B-cell differentiation stage. This work shows that B-cells in blood and gut of patients with Crohn's disease are at an advanced stage of differentiation based on their unusual presentation of transitional (RA+ RO+) and late stage (RO+)CD45 isoforms on lamina propria lymphocytes, whereas normal intestinal lamina propria lymphocytes B-cells express primarily CD45RA. Crohn's disease patients had heightened expression of the CD45RO isoform on CD19+ lamina propria lymphocytes, and was found in a statistically significant proportion of Crohn's peripheral blood mononuclear cells (PBMC) where CD19+ PBMC had an expression pattern affecting an unexpectedly high proportion of these differentiated or late stage CD45RO+ B-cells. The expression of CD45RO varied greatly among CD19+ PBMC from patients with Crohn's disease, so multiple regression analysis was performed between these CD45 isoforms and several clinical parameters. After grouping high and low CD45RO expression on CD19+ B-cells, a significant statistical difference was found between high Crohn's disease activity index (CDAI) and low CDAI Crohn's disease patients respectively. PMID:7506695
Buchel, O C; Bosch, F J; Janse van Rensburg, J; Bezuidenhout, E; de Vries, C S; van Zyl, J H; Middlecote, B D; de K Grundling, H; Fevery, J
Crohn's disease is rare in South African black people and primary sclerosing cholangitis (PSC) is also rare in black patients with IBD, from South Africa. The presence of HLA-B27 is generally associated with seronegative spondylo-arthropathies and correlates with the occurrence of ankylosing spondylitis, recurrent mouth ulcers and uveitis, in patients with IBD. We describe two women with the combination of Crohn's disease, PSC and HLA-B27 from our cohort of the last 5 years of three black patients with Crohn's disease. Crohn's disease, PSC and HLA-B27 respectively, occur rarely in black South Africans and their concurrent presence in two black women suggests a pathogenetic link of HLA-B27 between Crohn's disease and PSC in this population. Female gender might be an additional determinant in this setting.
Raynor, Eileen M
In the limited number of Crohn disease cases involving the head and neck, there is a predilection for mucosal surfaces and rare reports of involvement in the postauricular region. To our knowledge, in all previously reported cases involving the head and neck, the patients had a known diagnosis of Crohn disease. This case describes a 10-year-old boy with a history of psoriasis and psoriasiform dermatitis who presented with bilateral chronic granulomatous otitis externa, obliteration of the external auditory canal, and fissuring, resulting in separation of the lobule from the preauricular skin. Pathologic examination results were consistent with granulomatous dermatitis concerning for cutaneous Crohn disease, and a subsequent gastroenterologic workup confirmed the diagnosis of Crohn disease. This is a report of chronic granulomatous otitis as the initial presentation of cutaneous Crohn disease in a child.
Boltin, Doron; Levi, Zohar; Halpern, Marisa; Fraser, Gerald M
Adenocarcinomas of the large and small bowel, as well as intestinal carcinoid tumors have been reported at increased rates in Crohn's disease. We herein report a rare case of concurrent adenocarcinoma and carcinoid tumor of the small bowel presenting as intestinal obstruction and found incidentally at laparotomy in a 55 year old male with longstanding ileal Crohn's disease. We performed a Medline Pubmed search for cases of synchronous or composite adenocarcinoma and carcinoid tumor in the setting of Crohn's disease and identified four similar cases. Concurrent adenocarcinoma and carcinoid tumor occurred both in newly diagnosed and longstanding Crohn's disease, most commonly involved the terminal ileum and presented with symptoms mimicking Crohn's disease. Diagnosis was made incidentally at laparotomy in all cases. Lymph node involvement was variable. Clinicians should be aware of this rare entity for expeditious surgical intervention.
Limketkai, Berkeley N; Parian, Alyssa M; Shah, Neha D; Colombel, Jean-Frédéric
Crohn's disease is a chronic and progressive inflammatory disorder of the gastrointestinal tract. Despite the availability of powerful immunosuppressants, many patients with Crohn's disease still require one or more intestinal resections throughout the course of their disease. Multiple resections and a progressive reduction in bowel length can lead to the development of short bowel syndrome, a form of intestinal failure that compromises fluid, electrolyte, and nutrient absorption. The pathophysiology of short bowel syndrome involves a reduction in intestinal surface area, alteration in the enteric hormonal feedback, dysmotility, and related comorbidities. Most patients will initially require parenteral nutrition as a primary or supplemental source of nutrition, although several patients may eventually wean off nutrition support depending on the residual gut anatomy and adherence to medical and nutritional interventions. Available surgical treatments focus on reducing motility, lengthening the native small bowel, or small bowel transplantation. Care of these complex patients with short bowel syndrome requires a multidisciplinary approach of physicians, dietitians, and nurses to provide optimal intestinal rehabilitation, nutritional support, and improvement in quality of life.
Nuzzo, Alexandre; Zappa, Magaly; Cazals-Hatem, Dominique; Bouhnik, Yoram
Abstract Background: Mesenteric panniculitis (MP) is mostly an associated sign of an intra-abdominal or systemic inflammatory primary disease. Nevertheless, etiological and differential diagnosis of idiopathic MP can be challenging when an associate primary cause is not in the foreground. Methods: We report here the case of an isolated small bowel Crohn's disease, long time considered as idiopathic MP. Results: This patient presented to our department with a 10-year history of acute abdominal symptoms evolving with flare-up and remission. A diagnosis of idiopathic MP was made based on compatible CT-scan features along with normal laboratory tests and upper and lower bowel endoscopies. As symptoms recurred, a steroid course was proposed which dramatically improved his condition for years. Finally, an explorative laparoscopy was performed because of concern of malignancy when he returned to our unit with a steroid refractory flare-up and weight loss, along with MP nodes growing up to 10 mm. Crohn's disease was eventually diagnosed, based on histopathological middle-gut bowel resection and numerous granulomas in mesenteric nodes without necrosis. Conclusion: This case emphasizes the importance of excluding inflammatory intestinal lesions before making the diagnosis of idiopathic MP (fecal calprotectin, magnetic resonance enterography, wireless capsule endoscopy). PMID:27684882
Pierce, Ellen S.
Mycobacterium avium subspecies paratuberculosis (MAP) causes a chronic granulomatous inflammation of the intestines, Johne's disease, in dairy cows and every other species of mammal in which it has been identified. MAP has been identified in the mucosal layer and deeper bowel wall in patients with Crohn's disease by methods other than light microscopy, and by direct visualization in small numbers by light microscopy. MAP has not been accepted as the cause of Crohn's disease in part because it has not been seen under the microscope in large numbers in the intestines of patients with Crohn's disease. An analysis of the literature on the pathology of Crohn's disease and on possible MAP infection in Crohn's patients suggests that MAP might directly infect endothelial cells and adipocytes and cause them to proliferate, causing focal obstruction within already existing vessels (including granuloma formation), the development of new vessels (neoangiogenesis and lymphangiogenesis), and the “creeping fat” of the mesentery that is unique in human pathology to Crohn's disease but also occurs in bovine Johne's disease. Large numbers of MAP might therefore be found in the mesentery attached to segments of intestine affected by Crohn's disease rather than in the bowel wall, the blood and lymphatic vessels running through the mesentery, or the mesenteric fat itself. The walls of fistulas might result from the neoangiogenesis or lymphangiogenesis that occurs in the bowel wall in Crohn's disease and therefore are also possible sites of large numbers of MAP. The direct visualization of large numbers of MAP organisms in the tissues of patients with Crohn's disease will help establish that MAP causes Crohn's disease. PMID:19325887
Johne's disease is chronic inflammation of the intestine caused by Mycobacterium avium subspecies paratuberculosis. Infection and disease are mainly in domestic livestock but can affect many species including primates. Johne's is a new disease which emerged at the turn of the 19th and 20th centuries and principally involved Europe and North America. It has since spread to former low incidence regions to become a global problem. Crohn's disease is a chronic inflammation of the intestine in humans which emerged in Europe and North America mid 20th century and increased to become a major healthcare problem. It has now spread to former low incidence regions. Infected animals shed Mycobacterium avium subspecies paratuberculosis in milk and into the environment. Human populations are widely exposed. Outcomes maybe influenced by microbial phenotype. Exposure to extracellular forms of these pathogens may confer some natural protection; exposure to intracellular forms which have passaged through milk macrophages or environmental protists may pose a greater threat to humans particularly individuals with an inherited or acquired susceptibility. Hot spots of human disease such as in Winnipeg which sits on rock at the junction of two rivers may result from local exposure to high levels of waterborne pathogens brought down from farmland. When appropriate methods are used most people with Crohn's disease are found to be infected. There are no data which demonstrate that these pathogens are harmless to humans. An overwhelming balance of probability and Public health risk favours the conclusion that Mycobacterium avium subspecies paratuberculosis is also pathogenic for people. A two tier co-operative pathogenic mechanism is proposed in Crohn's disease. Intracellular infection with the primary pathogen widely distributed throughout the gut causes an immune dysregulation and a specific chronic enteric neuropathy with loss of mucosal integrity. Segments of gross inflammatory disease
Liu, Song; Ding, Jie; Wang, Meng; Zhou, Wanqing; Feng, Min; Guan, Wenxian
Abstract Extraintestinal manifestations (EIMs) cause increased morbidity and decreased quality of life in Crohn disease (CD). Ankylosing spondylitis (AS) belongs to EIMs. Very little is known on the clinical features of CD concomitant with AS. This study is to investigate the clinical features of CD patients with AS. We retrospectively collected all CD patients with AS in our hospital, and established a comparison group (CD without AS) with age, sex, and duration of Crohn disease matched. Clinical information was retrieved for comparison. Eight CD + AS patients were identified from 195 CD patients. Sixteen CD patients were randomly selected into comparison group. All CD + AS patients were male, HLA-B27 (+), and rheumatoid factor (−) with an average age of 40.8 ± 4.52 years. Significant correlation between disease activity of CD and AS was revealed (r = 0.857, P = 0.011). Significant correlation between disease activity of CD and functional limitation associated with AS was identified (r = 0.881, P < 0.01). C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and globulin were positively correlated to Crohn disease activity index (CDAI), Bath AS disease activity index, and Bath AS functional index(BASFI) scores (r = 0.73–0.93, P < 0.05). Albumin was negatively associated with CDAI and BASFI (r = −0.73 to −0.91, P < 0.05). The ratio of albumin to globulin (Alb/Glo) was significantly related to all 3 scores (r = −0.81 to −0.91, P < 0.05). Male predominance with a 4.12% concomitant incidence of AS is observed in CD patients. Disease activity of CD correlates with disease activity of AS and functional limitation caused by AS. CRP, ESR, and Alb/Glo may serve as biomarkers for disease activity and functional limitation in CD patients concomitant with AS, although future studies are expected. PMID:27428240
Gerard, Romain; Sendid, Boualem; Colombel, Jean-Frederic; Poulain, Daniel; Jouault, Thierry
The etiology of Crohn's disease (CD), an autoimmune, inflammatory bowel disease (IBD) which affects approximately one million people in Europe, is still unclear. Nevertheless, it is widely accepted that CD could result from an inappropriate inflammatory response to intestinal microorganisms in a genetically susceptible host. Most studies to date have concerned the involvement of bacteria in disease progression. In addition to bacteria, there appears to be a possible link between the commensal yeast Candida albicans and disease development. In this review, in an attempt to link the gut colonization process and the development of CD, we describe the different pathways that are involved in the progression of CD and in the host response to C. albicans, making the yeast a possible initiator of the inflammatory process observed in this IBD.
Cançado, Guilherme Grossi Lopes; Vilela, Eduardo Garcia
We report the case of a 64-year-old patient diagnosed with extensive ileal Crohn´s disease who developed Guillain-Barré syndrome after starting biological therapy with adalimumab. Neurologic involvement associated with inflammatory bowel diseases is recognized as an extra-intestinal manifestation. After the breakthrough of antitumor necrosis factor alpha (anti-TNF-α) agents, an increasing number of cases of acute inflammatory demyelinating polyneuropathies have been reported; however, only one case has been described in a patient with Crohn´s disease. Although a causal relationship between Guillain-Barré syndrome and TNF-α antagonist therapy cannot be proven, this report emphasizes the need to monitor for neurologic signs and symptoms in patients with inflammatory bowel diseases, with or without biological therapy, to avoid severe and irreversible complications associated with demyelinating diseases.
Layden, T; Rosenberg, F; Nemchausky, G; Elson, C; Rosenberg, I
Growth arrest and delayed onset of puberty often complicate childhood onset Crohn's disease of the small bowel (granulomatous enteritis). Nutritional deficits arising from inadequate dietary intake, malabsorption, and increased caloric needs may contribute to growth retardation. To assess whether a sustained high caloric and nitrogen intake could reestablish growth, 4 children with extensive Crohn's disease of the small bowel were studied before and after parenteral alimentation which was instituted for symtomatic disease control. Weight gain, positive nitrogen balance, and improved nutritional status were achieved during parenteral alimentation in each patient. In 2 patients weight gain was sustained using oral nutritional supplements, and a substantial increase in linear skeletal growth continued in the ensuing months. One patient entered puberty within 4 months of parenteral alimentation and another had the onset of menarche and the development of secondary sex characteristics 4 months after parenteral alimentation and resection of diseased bowel. Growth may be reestablished in some growth-arrested children if intake is sufficient to establish a sustained positive caloric and nitrogen balance. Nutritional requirements imposed by the demands of growth and active disease and often compounded by the catabolic effects of corticosteroids may be excessive; growth may occur only if these needs are met orally and/or parenterally.
Juillerat, Pascal; Pittet, Valérie; Mottet, Christian; Felley, Christian; Gonvers, Jean-Jacques; Vader, John-Paul; Burnand, Bernard; Froehlich, Florian; Wolters, Frank L; Stockbrügger, Reinhold W; Michetti, Pierre
The European Panel on the Appropriateness of Crohn's disease Therapy (EPACT) has developed appropriateness criteria. We have applied these criteria retrospectively to the population-based inception cohort of Crohn's disease (CD) patients of the European Collaborative Study Group on Inflammatory Bowel Disease (EC-IBD). A total of 426 diagnosed CD patients from 13 European centers were enrolled at the time of diagnosis (first flare, naive patients). We used the EPACT definitions to identify 247 patients with active luminal CD. We then assessed the appropriateness of the initial drug prescription according to the EPACT criteria. Among the cohort patients 163 suffered from mild-to-moderate CD and 84 from severe CD. Among the mild-to-moderate disease group, 96 patients (59%) received an appropriate treatment, whereas for 66 patients (40%) the treatment was uncertain and in one case (1%) inappropriate. Among the severe disease group, 86% were treated medically and 14% required surgery. 59 (70%) were appropriately treated, whereas for one patient (1%) the procedure was considered uncertain and for 24 patients (29%) inappropriate. Initial treatment was appropriate in the majority of cases for non-complicated luminal CD. Inappropriate or uncertain treatment was given in a significant minority of patients, with an increased potential risk of adverse events.
Bressler, Brian; Bethel, Kevin P.; Kleef, Ralf; Reynolds, Sophie L.; Sutcliffe, Simon; Mullins, David W.; Gunn, Hal
We investigated the mechanism of action, safety, and efficacy of the Site-Specific Immunomodulator (SSI) QBECO, a novel immunotherapy for Crohn's disease (CD). Using human monocytic THP-1 cells, we demonstrate that SSI QBECO (derived from the common colon bacteria E. coli) activates macrophages to an M1 phenotype (associated with enhanced capacity to eliminate bacteria and activate innate immune responses). We assessed SSI QBECO in a compassionate use protocol of ten adult patients with active CD. Patients with moderate to severe clinical symptoms receiving conventional CD treatments and/or complementary therapies were included, except patients receiving anti-TNF medications. SSI QBECO was self-administered subcutaneously every second day, for a minimum of 2.5 months and a maximum of 11 months. All 10 patients reported improvement of symptoms while on the SSI QBECO treatment. Seven patients reported full resolution of clinical symptoms during a course of SSI QBECO of at least three months. Three patients have experienced ongoing sustained clinical remission after discontinuing all medications, including SSI treatment. The longest case of clinical remission is still ongoing (>4 years). No serious severe adverse clinical events were reported. Collectively, we conclude that treatment with the immunoactive SSI QBECO was well tolerated and effective for treatment of Crohn's disease in this case series. PMID:26064087
Lescut, D; Vanco, D; Bonnière, P; Lecomte-Houcke, M; Quandalle, P; Wurtz, A; Colombel, J F; Delmotte, J S; Paris, J C; Cortot, A
The aim of this study was to search for small bowel lesions by means of a perioperative endoscopy in 20 patients operated on for Crohn's disease. Seven women and 13 men (mean age 29 years) had a total retrograde exploration to the angle of Treitz during an ileocolectomy (16 of 20 patients) or a colonic or ileal resection (four of 20 patients). Endoscopic exploration was completed, through an enterotomy, from the surgical area to the angle of Treitz. Periendoscopic biopsy samples were taken on macroscopic lesions and every 20 cm systematically. In 13 of 20 cases, various lesions scattered over the whole small intestine were found. These were aphthoid ulcerations (10 patients), superficial ulcerations (seven patients), mucosal oedema (three patients), non-ulcerative stenosis (three patients), erythema (two patients), pseudopolyps (two patients), deep ulcerations (two patients), and ulcerative stenosis (one patient). In seven patients none of the lesions detected at perioperative endoscopy had been recognised by preoperative evaluation or surgical inspection of the serosal surface. A typical granuloma was found at biopsy of lesions identified by endoscopy in three cases and at biopsy of an apparently healthy area in one case. Thus 65% of patients operated on for Crohn's disease had lesions of the small intestine detected by endoscopy, which were unrecognised before surgery in more than half of the cases. PMID:8504965
A computed tomographic (CT) analysis of 36 patients with differential diagnosis of intestinal tuberculosis (IT) or Crohn's disease (CD) in barium gastrointestinal studies was undertaken to identify distinguishing bowel wall or mesenteric features which could provide a radiological definitive diagnosis. Final diagnoses obtained in 32 cases were tuberculosis (N = 18), CD (N = 9), carcinoid (N = 2), chronic appendicitis (N = 2) and bowel infarction (N = 1). In IT, the bowel wall changes were varied: absence of wall thickening (N = 6), minimal asymmetric wall thickening with and without mucosal tethering (N = 8), minimal symmetric wall thickening often with mild peritonitis (N = 3), exophytic mass encircling bowel lumen (N = 4). Mural stratification (target sign) was not found. CD showed concentric or symmetrical wall thickening ranging from 0.6 to 1.5 mm and mural stratification occurred in about a half of the cases. Lymphadenopathy was the commonest associated feature in both but in IT, the nodes were larger and a third had necrotic centers. Displacement of bowel loops was more often due to enlarged lymphadenopathy in IT while in CD it was frequently due to fibrofatty change. CT was able to provide the correct diagnosis in 26 out of these 32 (81%) cases of indeterminate barium studies. CT is recommended when barium gastrointestinal studies are unable to differentiate between intestinal tuberculosis and Crohn's disease.
Sturiale, Alessandro; Alemanno, Giovanni; Giudici, Francesco; Addasi, Rami; Bellucci, Francesco; Tonelli, Francesco
INTRODUCTION The Median Arcuate Ligament Syndrome is a rare condition characterized by postprandial abdominal pain, bowel function disorder and weight loss. We report the first case to our knowledge of Crohn's disease and Median Arcuate Ligament Syndrome. PRESENTATION OF CASE The patient was a 33 year-old female with a previous diagnosis of Crohn's disease. Acute postprandial abdominal pain affected the patient every day; she was, therefore, referred to US-Doppler and magnetic resonance angiography of the abdominal vessels and received a diagnosis of Median Arcuate Ligament Syndrome. Consequently, the patient was surgically treated, releasing the vascular compression. After the operation, she reported a complete relief from postprandial pain which was one of her major concerns. Subocclusive symptoms occurred after six months due to the inflammatory reactivation of the terminal ileitis. DISCUSSION The diagnosis of Median Arcuate Ligament Syndrome is mainly based on the exclusion of other intestinal disorders but it should be always confirmed using noninvasive tests such as US-Doppler, angio-CT or magnetic resonance angiography. CONCLUSION This case demonstrates that the Median Arcuate Ligament Syndrome could be the major cause of symptoms, even in presence of other abdominal disorders. PMID:23500743
Schultz, Michael; Timmer, Antje; Herfarth, Hans H; Sartor, R Balfour; Vanderhoof, Jon A; Rath, Heiko C
Experimental studies have shown that luminal antigens are involved in chronic intestinal inflammatory disorders such as Crohn's disease and ulcerative colitis. Alteration of the intestinal microflora by antibiotic or probiotic therapy may induce and maintain remission. The aim of this randomized, placebo-controlled trial was to determine the effect of oral Lactobacillus GG (L. GG) to induce or maintain medically induced remission. Eleven patients with moderate to active Crohn's disease were enrolled in this trial to receive either L. GG (2 x 10(9) CFU/day) or placebo for six months. All patients were started on a tapering steroid regime and received antibiotics for the week before the probiotic/placebo medication was initiated. The primary end point was sustained remission, defined as freedom from relapse at the 6 months follow-up visit. Relapse was defined as an increase in CDAI of >100 points. 5/11 patients finished the study, with 2 patients in each group in sustained remission. The median time to relapse was 16 +/- 4 weeks in the L. GG group and 12 +/- 4.3 weeks in the placebo group (p = 0.5). In this study we could not demonstrate a benefit of L. GG in inducing or maintaining medically induced remission in CD.
Rakitina, Daria V; Manolov, Alexander I; Kanygina, Alexandra V; Garushyants, Sofya K; Baikova, Julia P; Alexeev, Dmitry G; Ladygina, Valentina G; Kostryukova, Elena S; Larin, Andrei K; Semashko, Tatiana A; Karpova, Irina Y; Babenko, Vladislav V; Ismagilova, Ruzilya K; Malanin, Sergei Y; Gelfand, Mikhail S; Ilina, Elena N; Gorodnichev, Roman B; Lisitsyna, Eugenia S; Aleshkin, Gennady I; Scherbakov, Petr L; Khalif, Igor L; Shapina, Marina V; Maev, Igor V; Andreev, Dmitry N; Govorun, Vadim M
Escherichia coli (E. coli) has been increasingly implicated in the pathogenesis of Crohn's disease (CD). The phylogeny of E. coli isolated from Crohn's disease patients (CDEC) was controversial, and while genotyping results suggested heterogeneity, the sequenced strains of E. coli from CD patients were closely related. We performed the shotgun genome sequencing of 28 E. coli isolates from ten CD patients and compared genomes from these isolates with already published genomes of CD strains and other pathogenic and non-pathogenic strains. CDEC was shown to belong to A, B1, B2 and D phylogenetic groups. The plasmid and several operons from the reference CD-associated E. coli strain LF82 were demonstrated to be more often present in CDEC genomes belonging to different phylogenetic groups than in genomes of commensal strains. The operons include carbon-source induced invasion GimA island, prophage I, iron uptake operons I and II, capsular assembly pathogenetic island IV and propanediol and galactitol utilization operons. Our findings suggest that CDEC are phylogenetically diverse. However, some strains isolated from independent sources possess highly similar chromosome or plasmids. Though no CD-specific genes or functional domains were present in all CD-associated strains, some genes and operons are more often found in the genomes of CDEC than in commensal E. coli. They are principally linked to gut colonization and utilization of propanediol and other sugar alcohols.
Andre, F; Andre, C; Emery, Y; Forichon, J; Descos, L; Minaire, Y
The mannitol-lactulose intestinal permeability test was evaluated in 100 healthy controls and 47 patients with Crohn's disease. These patients were further separated into three subgroups of increased activity (Harvey-Bradshaw index) and in two subgroups, with elective colonic lesions and associated ileal and colonic lesions. Results were given as percentages of urinary recoveries for mannitol (M), lactulose (L), and L/M ratio. As a whole, patients with Crohn's disease have lower mean M and higher mean L and mean L/M ratios than controls. The magnitude of alterations in M, L, and L/M increased with activity. The sensitivity of the test, however, reached interesting figures (67%:L and 86%:L/M) only in subgroup III which was composed of relapsing patients. Mean M was lower in patients with associated ileal lesion but, whatever the criterion (M, L, or L/M), the test does not provide any clue for the detection of a possible infraclinical associated ileal localisation. PMID:3131194
Caddy, G. R.
Patients with Crohn's disease often require the use of immunosuppressant drugs to control disease activity. Such medication includes steroids, azathioprine, and biologic therapy. These suppress the immune response, and the patient is more susceptible to infection. We present a case of a 69-year-old gentleman with a history of Crohn's colitis who had ongoing symptoms of diarrhoea in spite of standard treatment. Biologic therapy was considered to be the next step, and screening for infection was undertaken prior to use. Three days following anti-TNF treatment, he became drowsy, and examination revealed pyrexia, slurred speech, and nystagmus. Investigation revealed presence of Listeria rhombencephalitis. He demonstrated poor neurological recovery. Listeria monocytogenes is an infection commonly associated with food sources. Some patients develop a self-limiting diarrhoeal illness, but in the immunosuppressed population, the clinical features may be more sinister. Cotrimoxazole prophylaxis is already recommended for those on triple immunosuppression. We propose the early initiation of this treatment, including where biologic use is anticipated. In those on multiple immunosuppressants, a diet similar to that followed in pregnancy may minimise risk of acquiring this infection. Clinicians must always have a high index of suspicion for opportunistic infection in such immunocompromised patients. PMID:27651962
Rhodes, J M; Gallimore, R; Elias, E; Allan, R N; Kennedy, J F
Because the normal faecal flora includes bacteria which can produce mucus-digesting glycosidases, it follows that increased digestion of colonic mucus by these bacterial enzymes could be important in the pathogenesis of ulcerative colitis. Faecal activities of potential mucus-degrading glycosidases have therefore been assayed in samples from patients with inflammatory bowel disease and normal controls. The enzymes alpha-D-galactosidase, beta-D-galactosidase, beta-NAc-D-glucosaminidase alpha-L-fucosidase and neuraminidase were assayed. Considerable glycosidase activity was present in most faecal samples. Similar activities of all the enzymes assayed were found in faeces from patients with ulcerative colitis, Crohn's disease and normal controls and there was no significant correlation with disease activity. These results imply that relapse of ulcerative colitis is not initiated by increased degradation of colonic mucus by faecal glycosidases but do not exclude a role for bacterial mucus degradation in the pathogenesis of ulcerative colitis.
Luján-Sanchis, Marisol; Sanchis-Artero, Laura; Larrey-Ruiz, Laura; Peño-Muñoz, Laura; Núñez-Martínez, Paola; Castillo-López, Génesis; González-González, Lara; Clemente, Carlos Boix; Albert Antequera, Cecilia; Durá-Ayet, Ana; Sempere-Garcia-Argüelles, Javier
Capsule endoscopy (CE) currently plays an important role in Crohn's disease (CD). It is a noninvasive technique that has led to a breakthrough in the endoscopic diagnosis of diseases of the small intestine. Its superior diagnostic performance and excellent safety profile lead to its considerable acceptance on the part of the patient. This paper reviews current indications of CE in three stages of clinical practice: Suspected CD, unclassified colitis and its extensive role in diagnosed CD. The diagnostic and therapeutic impact of the results of CE on the monitoring of this disease is also reviewed. Knowledge of its applications, the interpretation of its results in an appropriate context and the existence of a validated endoscopic activity index could change the way in which these patients are managed. The definition of mucosal healing and postoperative recurrence by means of endoscopic scoring systems will endow CE with new applications in the management of CD in the near future.
Botti, F; Losco, A; Viganò, C; Oreggia, B; Prati, M; Contessini Avesani, E
Crohn's disease is a chronic inflammatory disease which may involve any segment of the gastrointestinal tract, most frequently the terminal ileum, the large intestine, and the perianal region. The symptoms of perianal Crohn's disease include skin disorders, hemorrhoids, anal ulcers, anorectal stenosis, perianal abscesses and fistulas, rectovaginal fistulas and carcinoma of the perianal region. The perianal manifestations of Crohn's disease cause great discomfort to the patient and are among the most difficult aspects to treat. Management of perianal disease requires a combination of different imaging modalities and a close cooperation between gastroenterologists and dedicated surgeons.
Joseph, A J; George, Biju; Pulimood, A B; Seshadri, M S; Chacko, Ashok
Western studies show that up to 65 per cent of patients with Crohn's disease have low serum 25-hydroxy vitamin D concentrations, and 45 per cent of these patients have metabolic bone disease. No data are available from India or from any country with comparable climatic conditions or ethnicity. We carried out this study to measure the serum 25 (OH) vitamin D levels of Crohn's disease patients and compare with matched controls and to assess the consequences of low 25 (OH) vitamin D levels on bone and mineral metabolism in these patients. Adult patients with Crohn's disease were compared with age and sex matched patients diagnosed to have irritable bowel syndrome. Serum 25 (OH) vitamin D, the effect of disease characteristics, sunlight exposure and milk consumption on 25 (OH) vitamin D level, and the consequences of low 25 (OH) vitamin D level on bone and mineral metabolism were assessed. Thirty four patients with Crohn's disease (M:F, 24:10, age 39.2 +/- 12.9 yr) and 34 controls (M:F, 24:10, age 38.9 +/- 13.4 yr) were studied. 25 (OH) vitamin D levels were significantly lower in patients with Crohn's disease as compared to controls (Crohn's disease vs controls: 16.3 +/- 10.8 vs 22.8 +/- 11.9 ng/ml; P<0.05). The severity of disease activity as assessed by the Harvey Bradshaw score correlated negatively (Correlation coefficient -0.484, significance P<0.004), and the duration of sunlight exposure correlated positively (Correlation coefficient 0.327, significance P=0.007) with the serum 25 (OH) vitamin D level. Serum 25 (OH) vitamin D levels were significantly lower among patients with Crohn's disease as compared to age and sex matched controls. Further, 25 (OH) vitamin D levels in patients with Crohn's disease were lower in those with severe disease activity and less sun exposure. Further studies need to be done to correlate low 25 (OH) vitamin D level with bone density and assess the effect of vitamin D supplementation in these patients.
Morin, C L; Roulet, M; Roy, C C; Weber, A; Lapointe, N
Ten pediatric patients, aged 8.5-19 years, with active symptomatic Crohn's disease, received a three-week period of continuous elemental enteral alimentation with no other form of treatment. All patients in this study were selected according to the following criteria, which were applied consecutively: (1) newly diagnosed patients with no previous treatment for Crohn's disease, (2) disease activity index over 200, and (3) no complication requiring surgery. All patients experienced a clinical remission and improved their immunologic and nutritional status during the elemental enteral alimentation. The mean disease activity index for the whole group was 307.0 +/- 23.6 (range: 203 to 413) before and 69.2 +/- 11.4 (range: 15 to 114) after the feeding period. Significant increases in body weight, triceps skinfold, mid-arm circumference, serum transferrin and mean percentage of T lymphocytes were also observed. Following cessation of enteral alimentation, a small declining dose of prednisone was used during a one-year follow-up period. Eight of the ten patients were still in clinical remission three months after the feeding period and their nutritional status had continued to improve during that period of time.
Kanaan, Ziad; Ahmad, Surriya; Bilchuk, Natalia; Vahrenhold, Crystal; Pan, Jianmin; Galandiuk, Susan
To investigate genotype-phenotype correlations in patients with perianal Crohn's disease (PCD) in order to determine which factors predispose to development of perianal disease in Crohn's patients. Seven-hundred and ninety-five Caucasian individuals (317 CD patients and 478 controls without inflammatory bowel disease, IBD) were prospectively enrolled into a clinical/genetic database. Demographic and clinical data, as well as peripheral blood leukocyte DNA were obtained from all patients. The following were evaluated: three NOD2/CARD15 polymorphisms: R702W, G908R, and 1007insC; five IL-23r risk alleles: rs1004819, rs10489629, rs2201841, rs11465804, and rs11209026; a well-characterized single-nucleotide polymorphism (SNP) on the IBD5 risk haplotype (OCTN1) and two peripheral tag SNPs (IGR2060 and IGR3096). PCD occurred in 147 (46%) of CD patients. There was no significant difference in the age at disease diagnosis between non-PCD and PCD patients (33 vs. 29 years, respectively). PCD patients were more likely to have disease located in the colon and ileocolic regions (79 PCD vs. 57% non-PCD; n = 116 vs. n = 96; p < 0.001), whereas patients with non-PCD were more likely to have Crohn's within the terminal ileum and upper gastrointestinal tract (43% non-PCD vs. 21% PCD; n = 73 vs. n = 31; p < 0.05). Thirty-four percent of patients with PCD required a permanent ileostomy (n = 50) compared to only 4% of non-PCD patients (n = 6; p < 0.05). Mutations in CARD15/NOD2 and IL-23r were risk factors for CD overall; however, in contrast to prior reports, in this patient population, OCTN1 and IGR variations within the IBD5 haplotype were not significant predictors of PCD. Colon/ileocolic CD location appears to be a significant predictor of perianal manifestations of CD. Patients with PCD are more likely to require permanent fecal diversion. We did not identify any genetic variations or combination of clinical findings and genetic variations within the CARD15/NOD2, IL-23r, and OCTN1
Han, Yoo Min; Kim, Ji Won; Koh, Seong-Joon; Kim, Byeong Gwan; Lee, Kook Lae; Im, Jong Pil; Kim, Joo Sung; Jung, Hyun Chae
The presence of perianal disease in Crohn's disease patients is one of the factors of postoperative recurrence. The aim of this study is to evaluate long-term prognosis of perianal Crohn's disease patients in Asian. Patients with Crohn's disease who had undergone surgical bowel resection were divided into two groups according to the presence of perianal lesion. We monitored the occurrences of abdominal and/or perianal reoperation and readmission due to disease flare-up. The 132 patients included in the study were divided into 2 groups, those with perianal disease (45 patients, 34.1%) and those without perianal disease (87 patients, 65.9%). Patients with perianal disease was younger in age (33.8 years versus 39.8 years, p = 0.015) and had been diagnosed as CD at a younger age (21.9 years versus 28.6 years, p = 0.005) than patients without perianal disease. Patients with perianal disease showed more extra-intestinal manifestation than patients without perianal disease (8 versus 3, p = 0.008). Reoperation was required in 46 (44.8%) patients during the follow-up period. The presence of perianal disease independently increased the risk of reoperation [hazard ratio (HR), 3.112; confidence interval (CI), 1.707-5.675]. Furthermore, patients with perianal disease had increasing risks of abdominal reoperation (HR 1.978; 95% CI, 1.034-3.784). Patients with Crohn's disease and perianal lesions had a higher risk of reoperation. Considering these findings, physicians should consider aggressive and early top down therapy for patients with perianal Crohn's disease. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
Gasparetto, Marco; Guariso, Graziella
Nutritional concerns, linear growth deficiency, and delayed puberty are currently detected in up to 85% of patients with Crohn's disease (CD) diagnosed at childhood. To provide advice on how to assess and manage nutritional concerns in these patients, a Medline search was conducted using "pediatric inflammatory bowel disease", "pediatric Crohn's disease", "linear growth", "pubertal growth", "bone health", and "vitamin D" as key words. Clinical trials, systematic reviews, and meta-analyses published between 2008 and 2013 were selected to produce this narrative review. Studies referring to earlier periods were also considered if the data was relevant to our review. Although current treatment strategies for CD that include anti-tumor necrosis factor-α therapy have been shown to improve patients' growth rate, linear growth deficiencies are still common. In pediatric CD patients, prolonged diagnostic delay, high initial activity index, and stricturing/penetrating type of behavior may cause growth deficiencies (in weight and height) and delayed puberty, with several studies reporting that these patients may not reach an optimal bone mass. Glucocorticoids and inflammation inhibit bone formation, though their impact on skeletal modeling remains unclear. Long-term control of active inflammation and an adequate intake of nutrients are both fundamental in promoting normal puberty. Recent evidence suggests that recombinant growth factor therapy is effective in improving short-term linear growth in selected patients, but is of limited benefit for ameliorating mucosal disease and reducing clinical disease activity. The authors conclude that an intense initial treatment (taking a "top-down" approach, with the early introduction of immunomodulatory treatment) may be justified to induce and maintain remission so that the growth of children with CD can catch up, ideally before puberty. Exclusive enteral nutrition has a key role in inducing remission and improving patients
Koutroumpakis, Efstratios; Katsanos, Konstantinos H.
Simple Endoscopic Score for Crohn's Disease (SES-CD) was developed as an attempt to simplify Crohn's Disease Endoscopic Index of Severity (CDEIS). Since it was constructed from CDEIS, SES-CD performs comparably but also carries similar limitations. Several studies have utilized SES-CD scoring to describe disease severity or response to therapy. Some of them used SES-CD score as a continuous variable while others utilized certain cutoff values to define severity grades. All SES-CD cutoff values reported in published clinical trials were empirically selected by experts. Although in most of the studies that used SEC-CD scoring to define disease severity, a score <3 reflected inactive disease, no study is using score 0 to predefine inactivity. Studies applying SES-CD to define response to treatment used score 0. There is no optimal SES-CD cut-off for endoscopic remission. The quantification of mucosal healing using SES-CD scoring has not been standardized yet. As the definition of mucosal healing by SES-CD is unset, the concept of deep remission is also still evolving. Serum and fecal biomarkers as well as new radiologic imaging techniques are complementary to SES-CD. Current practice as well as important changes in endoscopy should be taken into consideration when defining SES-CD cutoffs. The optimal timing of SES-CD scoring to assess mucosal healing is not defined yet. To conclude, SES-CD represents a valuable tool. However, a consensus agreement on its optimal use is required. PMID:27184635
Hatch, Quinton; Champagne, Bradley J; Maykel, Justin A; Davis, Bradley R; Johnson, Eric K; Bleier, Joshua I; Francone, Todd D; Steele, Scott R
The impact of pregnancy on the course of Crohn disease is largely unknown. Retrospective surveys have suggested a variable effect, but there are limited population-based clinical data. We hypothesized pregnant women with Crohn disease will have similar rates of surgical disease as a nonpregnant Crohn disease cohort. International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify female Crohn patients from all patients admitted using the Nationwide Inpatient Sample (1998-2009). Women were stratified as either pregnant or nonpregnant. We defined Crohn-related surgical disease as peritonitis, gastrointestinal hemorrhage, intra-abdominal abscess, toxic colitis, anorectal suppuration, intestinal-intestinal fistulas, intestinal-genitourinary fistulas, obstruction and/or stricture, or perforation (excluding appendicitis). Of the 92,335 women admitted with a primary Crohn-related diagnosis, 265 (0.3%) were pregnant. Pregnant patients were younger (29 versus 44 y; P<0.001) and had lower rates of tobacco use (6% versus 13%; P<0.001). Pregnant women with Crohn disease had higher rates of intestinal-genitourinary fistulas (23.4% versus 3.0%; P<0.001), anorectal suppuration (21.1% versus 4.1%; P<0.001), and overall surgical disease (59.6% versus 39.2%; P<0.001). On multivariate logistic regression analysis controlling for malnutrition, smoking, age, and prednisone use, pregnancy was independently associated with higher rates of anorectal suppuration (odds ratio [OR], 5.2; 95% confidence interval [CI], 3.8-7.0; P<0.001), intestinal-genitourinary fistulas (OR, 10.4; 95% CI, 7.8-13.8; P<0.001), and overall surgical disease (OR, 2.9; 95% CI, 2.3-3.7; P<0.001). Pregnancy in women with Crohn disease is a significant risk factor for Crohn-related surgical disease, in particular, anorectal suppuration and intestinal-genitourinary fistulas. Published by Elsevier Inc.
Alfa-Wali, Maryam; Atinga, Angela; Mohsen, Yasser; Anthony, Andrew; Myers, Alistair
INTRODUCTION Fistulas are a relatively common occurrence in Crohn's disease (CD), and often present early in the disease process. Additionally, patients suffering from either CD or ulcerative colitis are shown to have an increased risk of colorectal malignancies compared with the general population. PRESENTATION OF CASE We present a case of adenocarcinoma in an ano-vaginal fistula in a patient with longstanding CD. DISCUSSION Various pathogenic mechanisms for the development of carcinoma in fistulas have been suggested, but there is no consensus and indeed this risk may be cumulative. In this case report, we also discuss the pathogenesis of mucinous adenocarcinoma in fistulas secondary to CD. CONCLUSION Better detection of adenocarcinoma in patients presenting with persistent non-resolving fistulas in the presence of CD should be undertaken with regular biopsies following examinations under anaesthetic of the anorectum. PMID:23702362
Mahapatra, Dwarikanath; Vos, Franciscus M; Buhmann, Joachim M
This paper proposes a novel active learning (AL) framework, and combines it with semi supervised learning (SSL) for segmenting Crohns disease (CD) tissues from abdominal magnetic resonance (MR) images. Robust fully supervised learning (FSL) based classifiers require lots of labeled data of different disease severities. Obtaining such data is time consuming and requires considerable expertise. SSL methods use a few labeled samples, and leverage the information from many unlabeled samples to train an accurate classifier. AL queries labels of most informative samples and maximizes gain from the labeling effort. Our primary contribution is in designing a query strategy that combines novel context information with classification uncertainty and feature similarity. Combining SSL and AL gives a robust segmentation method that: (1) optimally uses few labeled samples and many unlabeled samples; and (2) requires lower training time. Experimental results show our method achieves higher segmentation accuracy than FSL methods with fewer samples and reduced training effort. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Sica, Giuseppe S; Di Carlo, Sara; Tema, Giorgia; Montagnese, Fabrizio; Del Vecchio Blanco, Giovanna; Fiaschetti, Valeria; Maggi, Giulia; Biancone, Livia
Anal fistulas are a common manifestation of Crohn's disease (CD). The first manifestation of the disease is often in the peri-anal region, which can occur years before a diagnosis, particularly in CD affecting the colon and rectum. The treatment of peri-anal fistulas is difficult and always multidisciplinary. The European guidelines recommend combined surgical and medical treatment with biologic drugs to achieve best results. Several different surgical techniques are currently employed. However, at the moment, none of these techniques appear superior to the others in terms of healing rate. Surgery is always indicated to treat symptomatic, simple, low intersphincteric fistulas refractory to medical therapy and those causing disabling symptoms. Utmost attention should be paid to correcting the balance between eradication of the fistula and the preservation of fecal continence.
Tanabe, Hiroki; Ito, Takahiro; Inaba, Yuhei; Ando, Katsuyoshi; Nomura, Yoshiki; Ueno, Nobuhiro; Kashima, Shin; Moriichi, Kentaro; Fujiya, Mikihiro; Okumura, Toshikatsu
Endoscopic retrograde ileography (ERIG) is developed in our institute and applied clinically for the diagnosis and assessment of the Crohn's disease activity. We have further improved the technique using 3-dimensional - computed tomography enteroclysis (3D-CTE) and conducted a retrospective study to determine the feasibility and the diagnostic value of endoscopic retrograde 3D-CTE (ER 3D-CTE) in Crohn's disease patients in a state of remission. Thirteen Crohn's patients were included in this pilot study. CTE was performed after the infusion of air or CO2 through the balloon tube following conventional colonoscopy. The primary endpoint of this study was to assess the safety of this method. Secondarily, the specific findings of Crohn's disease and length of the visualized small intestine were assessed. The procedures were completed without any adverse events. Gas passed through the small intestine and enterographic images were obtained in 10 out of 13 cases, but, in the remaining patients, insertion of the balloon tubes into the terminal ileum failed. Various features specific to Crohn's disease were visualized using ER 3D-CTE. A cobble stone appearance or hammock-like malformation was specific and effective for diagnosing Crohn's disease and the features of anastomosis after the surgical operations were also well described. Therefore, this technique may be useful after surgery. In this study, ER 3D-CTE was performed safely in Crohn's disease patients and may be used for the diagnosis and follow-up of this disease.
Halme, L; Kärkkäinen, P; Rautelin, H; Kosunen, T U; Sipponen, P
The frequency of gastric Crohn's disease has been considered low. This study was undertaken to determine the prevalence of chronic gastritis and Helicobacter pylori infection in patients with Crohn's disease. Oesophagogastroduodenoscopy was performed on 62 consecutive patients suffering from ileocolonic Crohn's disease. Biopsy specimens from the antrum and corpus were processed for both histological and bacteriological examinations. H pylori antibodies of IgG and IgA classes were measured in serum samples by enzyme immunoassay. Six patients (9.7%) were infected with H pylori, as shown by histology, and in five of them the infection was also verified by serology. Twenty one patients (32%) had chronic H pylori negative gastritis (negative by both histology and serology) and one of them also had atrophy in the antrum and corpus. Granulomas were found in four patients. The characteristic appearance of H pylori negative gastritis was focal and mostly mild inflammation resembling the inflammatory changes seen in the gut in Crohn's disease. Patients with H pylori negative chronic gastritis had a significantly more active disease in their gut than those with normal gastric mucosa (p < 0.01). It is concluded that H pylori positive gastritis is rare, while H pylori negative gastritis is relatively common in patients with Crohn's disease. H pylori negative 'Crohn's gastritis' seems to be associated with active Crohn's disease. Images Figure 1 Figure 2 PMID:8675090
Buisine, M; Desreumaux, P; Leteurtre, E; Copin, M; Colombel, J; Porchet, N; Aubert, J
BACKGROUND—Crohn's disease (CD) is a chronic relapsing inflammatory bowel disease of unknown origin. It is characterised by chronic mucosal ulcerations which affect any part of the intestine but most commonly are found in the ileum and proximal colon. AIMS—Studies were undertaken to provide information regarding cell specific expression of mucin genes in the ileum of patients with CD. PATIENTS AND METHODS—Expression of mucin genes was analysed in the ileal mucosa of patients with CD and controls by in situ hybridisation and immunohistochemistry. RESULTS—In healthy ileal mucosa, patients with CD showed a pattern identical to normal controls with main expression of MUC2 and MUC3, lesser expression of MUC1 and MUC4, and no expression of MUC5AC, MUC5B, MUC6, or MUC7. In the involved mucosa, the pattern was somewhat comparable although heterogeneous to that observed in healthy ileal mucosa. Importantly, a particular mucin gene expression pattern was observed in ileal mucosa close to the ulcer margins in ulcer associated cell lineage, with the appearance of MUC5AC and MUC6 mRNAs and peptides, which are normally restricted to the stomach (MUC5AC and MUC6) and duodenum (MUC6), and disappearance of MUC2. CONCLUSIONS—Our results suggest that gel forming mucins (more particularly MUC5AC and MUC6) may have a role in epithelial wound healing after mucosal injury in inflammatory bowel diseases in addition to mucosal protection. Keywords: mucins; MUC genes; Crohn's disease; ulcer associated cell lineage PMID:11559653
Sanford, David; Thornley, Patrick; Teriaky, Anouar; Chande, Nilesh; Gregor, James
Quality of life is an important consideration in the management of patients with Crohn's disease. Previous studies suggest that Crohn's disease patients using opioids may have decreased quality of life and increased risk of mortality. Our aim was to determine the association between health-related quality of life (HRQoL) and opioid use in patients with Crohn's disease while controlling for disease severity. We conducted a cross-sectional study recruiting Crohn's disease patients at our center. Disease activity was measured using the Harvey-Bradshaw Index (HBI), and HRQoL was measured using the Inflammatory Bowel Disease Questionnaire (IBDQ). We enrolled 38 Crohn's disease patients using opioids and 62 patients not using opioids. Patients using opioids had an increased duration of disease (median 18.5 vs. 9 years, P = 0.005), increased surgeries related to Crohn's disease (median 3 vs. 0, P < 0.001), and increased prednisone use (29% vs. 11.3%, P = 0.03). Patients using opioids had increased disease activity (median HBI score 9.0 vs. 3.0, P < 0.001). Quality of life was lower in patients using opioids (mean IBDQ score 109.3 vs. 162.9, P < 0.001). This finding was significant when controlling for HBI scores, number of previous surgeries, and prednisone use (P = 0.003). Opioid use in Crohn's disease patients appears to be associated with disease activity and severity. HRQoL is markedly decreased in patients using opioids and this association is significant even when controlling for variables reflecting disease severity. Our findings suggest that Crohn's disease patients using opioids are likely to be significantly impacted by their disease.
Sanford, David; Thornley, Patrick; Teriaky, Anouar; Chande, Nilesh; Gregor, James
Background/Aims: Quality of life is an important consideration in the management of patients with Crohn's disease. Previous studies suggest that Crohn's disease patients using opioids may have decreased quality of life and increased risk of mortality. Our aim was to determine the association between health-related quality of life (HRQoL) and opioid use in patients with Crohn's disease while controlling for disease severity. Patients and Methods: We conducted a cross-sectional study recruiting Crohn's disease patients at our center. Disease activity was measured using the Harvey-Bradshaw Index (HBI), and HRQoL was measured using the Inflammatory Bowel Disease Questionnaire (IBDQ). Results: We enrolled 38 Crohn's disease patients using opioids and 62 patients not using opioids. Patients using opioids had an increased duration of disease (median 18.5 vs. 9 years, P = 0.005), increased surgeries related to Crohn's disease (median 3 vs. 0, P < 0.001), and increased prednisone use (29% vs. 11.3%, P = 0.03). Patients using opioids had increased disease activity (median HBI score 9.0 vs. 3.0, P < 0.001). Quality of life was lower in patients using opioids (mean IBDQ score 109.3 vs. 162.9, P < 0.001). This finding was significant when controlling for HBI scores, number of previous surgeries, and prednisone use (P = 0.003). Conclusions: Opioid use in Crohn's disease patients appears to be associated with disease activity and severity. HRQoL is markedly decreased in patients using opioids and this association is significant even when controlling for variables reflecting disease severity. Our findings suggest that Crohn's disease patients using opioids are likely to be significantly impacted by their disease. PMID:24976282
Levenstein, S; Prantera, C; Luzi, C; D'Ubaldi, A
Seventy patients with non-stenosing Crohn's disease were randomly assigned to follow a low residue diet or a normal Italian diet for a mean of 29 months. The two groups were comparable at the onset in various measures of disease severity and diet. Patients complied well with the diet prescriptions, the low residue group eating a mean of 8.1 portions a week of fibre containing foods and the liberalized group a mean of 26.6 portions (p less than 0.005). There was no difference in outcome between the two groups, including symptoms, need for hospitalisation, need for surgery, new complications, nutritional status, or postoperative recurrence. Eighty six per cent of patients eating ad libitum and 65% of patients who avoided roughage eliminated one or more permitted foods because of subjective intolerance. Lifting of dietary restrictions, which results in a more appetizing and nutritious diet, does not cause symptomatic deterioration or precipitate intestinal obstruction in Crohn's disease. PMID:2996991
Befrits, R; Hultcrantz, R
Despite extensive research, the cause of Crohn's disease remains unknown. No specific infectious agent has been identified, though interest has been focused on the possible involvement of mycobacteria, and recently on child hood measles as a possible aetiological factor. Both hereditary and environmental factors seem to contribute to development of the disease. The clinical picture may be dependent upon individual HLA subtypes, as they appear to differ from each other regarding the secretion of inflammatory cytokines. Non-invasive scintigraphy and computerised tomography are used to determine the extent of disease, and to localise such complications as abscesses and fistulas. Endoscopic ultrasonography and magnetic resonance imaging have proved particularly valuable in diagnosing rectal and rectovaginal fistulas. New 5-ASA (5-aminosalicylic acid) preparations, steroids with fewer systemic side effects, and azathioprine-induced immunosuppression constitute the cornerstones of medical treatment, further developments in pharmacological immunoregulation being a future treatment possibility.
De Cruz, Peter; Kamm, Michael A; Hamilton, Amy L; Ritchie, Kathryn J; Krejany, Efrosinia O; Gorelik, Alexandra; Liew, Danny; Prideaux, Lani; Lawrance, Ian C; Andrews, Jane M; Bampton, Peter A; Gibson, Peter R; Sparrow, Miles; Leong, Rupert W; Florin, Timothy H; Gearry, Richard B; Radford-Smith, Graham; Macrae, Finlay A; Debinski, Henry; Selby, Warwick; Kronborg, Ian; Johnston, Michael J; Woods, Rodney; Elliott, P Ross; Bell, Sally J; Brown, Steven J; Connell, William R; Desmond, Paul V
Most patients with Crohn's disease need an intestinal resection, but a majority will subsequently experience disease recurrence and require further surgery. This study aimed to identify the optimal strategy to prevent postoperative disease recurrence. In this randomised trial, consecutive patients from 17 centres in Australia and New Zealand undergoing intestinal resection of all macroscopic Crohn's disease, with an endoscopically accessible anastomosis, received 3 months of metronidazole therapy. Patients at high risk of recurrence also received a thiopurine, or adalimumab if they were intolerant to thiopurines. Patients were randomly assigned to parallel groups: colonoscopy at 6 months (active care) or no colonoscopy (standard care). We used computer-generated block randomisation to allocate patients in each centre to active or standard care in a 2:1 ratio. For endoscopic recurrence (Rutgeerts score ≥i2) at 6 months, patients stepped-up to thiopurine, fortnightly adalimumab with thiopurine, or weekly adalimumab. The primary endpoint was endoscopic recurrence at 18 months. Patients and treating physicians were aware of the patient's study group and treatment, but central reading of the endoscopic findings was undertaken blind to the study group and treatment. Analysis included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT00989560. Between Oct 13, 2009, and Sept 28, 2011, 174 (83% high risk across both active and standard care groups) patients were enrolled and received at least one dose of study drug. Of 122 patients in the active care group, 47 (39%) stepped-up treatment. At 18 months, endoscopic recurrence occurred in 60 (49%) patients in the active care group and 35 (67%) patients in the standard care group (p=0.03). Complete mucosal normality was maintained in 27 (22%) of 122 patients in the active care group versus four (8%) in the standard care group (p=0.03). In the active care arm
Weinstock, Leonard B.; Bosworth, Brian P.; Scherl, Ellen J.; Li, Ellen; Iroku, Ugonna; Munsell, Melissa A.; Mullen, Gerald E.; Walters, Arthur S.
Extraintestinal manifestations of Crohn's disease (CD) have not previously included the central nervous system (CNS). Restless legs syndrome (RLS) is a CNS disorder that is either idiopathic or secondary to a number of diseases. The aim of this study was to determine if RLS was associated with CD because both are associated with iron deficiency, inflammation, and bacterial overgrowth. Consecutive CD outpatients (N=272) were prospectively surveyed at 4 centers for criteria for RLS. Incidence (having RLS at any point in time), prevalence (having RLS at time of survey), clinical characteristics, risk factors, and potential qualitative relationship between RLS and gastrointestinal symptoms were queried. Incidence of RLS in patients with CD was 42.7%. Prevalence was 30.2% compared with 9% of spouses. Crohn's disease patients with and without RLS had a mean age of 46.8 vs 42.6 years, small intestine involvement in 77.9% vs 66.7%, colon involvement in 39.7% vs 63.2%, and prior iron deficiency anemia in 49.3% vs 33.1%. There was no difference between the CD groups with respect to current iron deficiency, RLS family history, or rare prevalence of concomitant RLS disorders. In 91.8% of patients with RLS and CD, RLS started during or after the onset of CD diagnosis. Among 73 patients with RLS, 67 (44.5%) stated there was a relationship between qualitative RLS symptom improvement with overall CD symptom improvement. These results demonstrate that RLS occurs frequently in CD and appears to be a possible extraintestinal manifestation. The potential relationship of RLS with CD activity warrants further investigation. PMID:19575360
El-Kersh, Karim; Fraig, Mostafa; Cavallazzi, Rodrigo; Saad, Mohamed; Perez, Rafael L
Pulmonary necrobiotic nodules represent a rare extra-intestinal manifestation of Crohn's disease. Histologically, they are composed of sterile aggregates of inflammatory cells with necrosis. The differential diagnosis is broad, and exclusion of infectious etiologies is mandatory before starting immunosuppressive therapy. Here, we present the fifth reported case of pulmonary necrobiotic nodules in Crohn's disease. Our patient had new-onset Crohn's disease associated with both cavitating and non-cavitating lung nodules that were confirmed to be necrobiotic nodules by biopsy. The patient was started on mesalamine and prednisone, with subsequent improvement of his gastrointestinal symptoms and regression of the necrobiotic nodules.
Neubauer, Henning; Pabst, Thomas; Dick, Anke; Machann, Wolfram; Evangelista, Laura; Wirth, Clemens; Köstler, Herbert; Hahn, Dietbert; Beer, Meinrad
Small-bowel MRI based on contrast-enhanced T1-weighted sequences has been challenged by diffusion-weighted imaging (DWI) for detection of inflammatory bowel lesions and complications in patients with Crohn disease. To evaluate free-breathing DWI, as compared to contrast-enhanced MRI, in children, adolescents and young adults with Crohn disease. This retrospective study included 33 children and young adults with Crohn disease ages 17 ± 3 years (mean ± standard deviation) and 27 matched controls who underwent small-bowel MRI with contrast-enhanced T1-weighted sequences and DWI at 1.5 T. The detectability of Crohn manifestations was determined. Concurrent colonoscopy as reference was available in two-thirds of the children with Crohn disease. DWI and contrast-enhanced MRI correctly identified 32 and 31 patients, respectively. All 22 small-bowel lesions and all Crohn complications were detected. False-positive findings (two on DWI, one on contrast-enhanced MRI), compared to colonoscopy, were a result of large-bowel lumen collapse. Inflammatory wall thickening was comparable on DWI and contrast-enhanced MRI. DWI was superior to contrast-enhanced MRI for detection of lesions in 27% of the assessed bowel segments and equal to contrast-enhanced MRI in 71% of segments. DWI facilitates fast, accurate and comprehensive workup in Crohn disease without the need for intravenous administration of contrast medium. Contrast-enhanced MRI is superior in terms of spatial resolution and multiplanar acquisition.
Zhang, Ai-jun; Zhan, Shu-hui; Chang, Hong; Gao, Yu-qiang; Li, Yan-qing
Crohn disease of the vulva is a rare disease that is difficult to diagnose. There are limited reports describing treatment of this condition. To describe the diagnosis and treatment of a 16-year-old girl with Crohn disease of the vulva, without onset of intestinal symptoms. Crohn disease was diagnosed by histopathology. The patient was treated with corticosteroids and followed for 1 year. After the final diagnosis, cutaneous lesions responded rapidly to corticosteroid treatment, which was gradually stopped after 6 months. The disease was well controlled at the 1-year follow-up. Crohn disease of the vulva can develop alone without the onset of intestinal symptoms. Diagnosis relies on special pathologic findings. Corticosteroid treatment is effective for this condition. © 2014 Canadian Dermatology Association.
Pierce, Ellen S
Mycobacterium avium, subspecies paratuberculosis (MAP) causes a chronic disease of the intestines in dairy cows and a wide range of other animals, including nonhuman primates, called Johne's ("Yo-knee's") disease. MAP has been consistently identified by a variety of techniques in humans with Crohn's disease. The research investigating the presence of MAP in patients with Crohn's disease has often identified MAP in the "negative" ulcerative colitis controls as well, suggesting that ulcerative colitis is also caused by MAP. Like other infectious diseases, dose, route of infection, age, sex and genes influence whether an individual infected with MAP develops ulcerative colitis or Crohn's disease. The apparently opposite role of smoking, increasing the risk of Crohn's disease while decreasing the risk of ulcerative colitis, is explained by a more careful review of the literature that reveals smoking causes an increase in both diseases but switches the phenotype from ulcerative colitis to Crohn's disease. MAP as the sole etiologic agent of both ulcerative colitis and Crohn's disease explains their common epidemiology, geographic distribution and familial and sporadic clusters, providing a unified hypothesis for the prevention and cure of the no longer "idiopathic" inflammatory bowel diseases.
Torregrosa, A; Pallardó, Y; Hinojosa, J; Insa, S; Molina, R
Radiology with oral contrast, or enteroclysis, have traditionally been the techniques of choice in the examination of the small intestine, due to the excellent visualisation of the mucosal pattern. However, the absence of extra-luminal information and the use of ionising radiation have replaced these examinations with sectional techniques which enable the abdominal cavity to be viewed with good resolution. Magnetic resonance enterography is a simple technique, with no ionising radiation, provided quality images, distends the intestinal lumen well by the administration of non-reabsorbable oral substances, minimises peristalsis, and establishes a protocol which includes sequences with intravenous contrast. These properties can be used in patients with Crohn's disease, achieving good diagnostic precision in the assessment of activity and monitoring of treatment, in intestinal obstruction, in the suspicion of small intestine tumours, and in paediatric patients due to it being harmless. Copyright © 2011 SERAM. Published by Elsevier Espana. All rights reserved.
Atienza, P; Ksiaa, M
All practitioners caring for patients with Crohn's disease (CD) must know all the various aspects of anoperineal lesions in this singular entity. Suppuration in CD does not follow the classic routes and spaces of diffusion and is often associated with endolumenal lesions that can evolve on their own. Abscesses and fistulas require specific medico-surgical management where seton drainage, staged operative and sphincter-sparing procedures have a dominant place. The variability of associated lesions and the particularly individualized efficacy of drugs call for case-by-case management, thus, making standardization and comparisons difficult. Recent therapeutic progress has led to modifications of the minimally invasive management policies practiced in the last decades.
Patedakis Litvinov, Bogdan Ioannis; Pathak, Amit P
We describe a case of a 23-year-old woman with a history of Crohn's disease (CD), who initially presented with sepsis-like symptoms, subsequently developed severe cholestasis and following extensive inpatient workup was found to have non-caseating granulomas on her liver biopsy. Infectious aetiologies were excluded and the patient was treated with oral corticosteroids, which ameliorated but did not completely reverse the cholestasis. We review the differential diagnosis of hepatic granulomas and discuss the potential difficulties in establishing their exact aetiology in patients with CD. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Khanna, Reena; Bressler, Brian; Levesque, Barrett G; Zou, Guangyong; Stitt, Larry W; Greenberg, Gordon R; Panaccione, Remo; Bitton, Alain; Paré, Pierre; Vermeire, Séverine; D'Haens, Geert; MacIntosh, Donald; Sandborn, William J; Donner, Allan; Vandervoort, Margaret K; Morris, Joan C; Feagan, Brian G
% CI -5·2% to 10·2%, p=0·5169). The 24 month patient-level composite rate of major adverse outcomes defined as occurrence of surgery, hospital admission, or serious disease-related complications was lower at ECI practices than at conventional management practices (27·7% and 35·1%, absolute difference [AD] 7·3%, hazard ratio [HR]: 0·73, 95% CI 0·62 to 0·86, p=0·0003). There were no differences in serious drug-related adverse events. Although ECI was not more effective than conventional management for controlling Crohn's disease symptoms, the risk of major adverse outcomes was lower. The latter finding should be considered hypothesis-generating for future trials. ECI was not associated with an increased risk of serious drug-related adverse events or mortality. AbbVie Pharmaceuticals. Copyright © 2015 Elsevier Ltd. All rights reserved.
Kroesen, A J
After colorectal and anorectal interventions for chronic inflammatory bowel diseases, specific complications can occur.In Crohn's disease these complications mainly occur after proctocolectomy. Pelvic sepsis can be prevented by omentoplasty with fixation inside the pelvis. A persisting sepsis of the sacral cavity can be treated primarily by dissection of the anal sphincter which ensures better drainage. In cases of chronic sacral sepsis, transposition of the gracilis muscle is a further effective option. Early recurrence of a transsphincteric anal fistula should be treated by reinsertion of a silicon seton drainage.Complications after restorative proctocolectomy are frequent and manifold (35%). The main acute complications are anastomotic leakage and pelvic sepsis. Therapy consists of transperineal drainage of the abscess with simultaneous transanal drainage. Late complications due to technical and septic reasons are still a relevant problem even 36 years after introduction of this operative technique. A consistent approach with detailed diagnostic and surgical therapy results in a 75% rescue rate of ileoanal pouches.
Unverdi, Selman; Ceri, Mevlut; Öztürk, Mehmet Akif; Akbal, Erdem; Ensari, Arzu; Yılmaz, Rahmi; Kocak, Erdem; Inal, Salih; Koklu, Seyfettin; Duranay, Murat
Thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS) is characterized with fever, purpura, anemia due to microangiopathic hemolysis, thrombocytopenia, kidney damage, and neurologic symptoms. The development of TTP/HUS during the course of inflammatory bowel diseases was rarely reported. However, coexistence of TTP/HUS and Crohn's disease in the same patient has not been reported previously. We herein present a case of TTP/HUS who presented with Crohn's disease. He responded to cyclosporine treatment.
Wright, Emily K.; Teo, Shu Mei; Inouye, Michael; Wagner, Josef; Kirkwood, Carl D.
Background: The intestinal microbiota is involved in the pathogenesis of inflammatory bowel disease. A reduction in the diversity of the intestinal microbiota as well as specific taxonomic and functional shifts have been reported in Crohn's disease and may play a central role in the inflammatory process. The aim was to systematically review recent developments in the structural and functional changes observed in the gastrointestinal microbiome in patients with Crohn's Disease. Results: Seventy-two abstracts were included in this review. The effects of host genetics, disease phenotype, and inflammatory bowel disease treatment on the gastrointestinal microbiome in Crohn's disease were reviewed, and taxonomic shifts in patients with early and established disease were described. The relative abundance of Bacteroidetes is increased and Firmicutes decreased in Crohn's disease compared with healthy controls. Enterobacteriaceae, specifically Eschericia coli, is enriched in Crohn's disease. Faecalibacterium prausnitzii is found at lower abundance in Crohn's disease and in those with postoperative recurrence. Observed functional changes include major shifts in oxidative stress pathways, a decrease in butanoate and propanoate metabolism gene expression, lower levels of butyrate, and other short-chain fatty acids, decreased carbohydrate metabolism, and decreased amino acid biosynthesis. Conclusions: Changes in microbial composition and function have been described, although a causative role remains to be established. Larger, prospective, and longitudinal studies are required with deep interrogation of the microbiome if causality is to be determined, and refined microbial manipulation is to emerge as a focused therapy. PMID:25844959
Vasilyeva, Ekaterina; Abdulkhakov, Sayar; Cherepnev, Georgi; Mayanskaya, Irina; Valeeva, Alina; Abdulkhakov, Rustam; Safina, Dilyara
Crohn's disease (CD) is a chronic inflammatory bowel disease that can be diagnosed at any age. There are two major patient groups based on diagnosis of this disease, before or after the age of 20 (juvenile/adolescent or adult), with disease progression in adults usually milder than in juvenile CD patients. Immune mechanisms have been suggested to play an important role in CD pathogenesis, with cytokines governing the development of the immune response. Upregulation of inflammatory cytokines in serum of juvenile and adult CD patients has been documented; still little is known about age-dependent differences in serum cytokine profiles of CD patients. We applied multiplex technology to analyze serum levels of 12 cytokines in juveniles and adults. We show that during the acute stage of the disease all CD patients have high serum levels of CXCL10, which remains upregulated during remission. Increased serum levels of TNF-α and IL-6 during the acute stage was characteristic of juvenile CD patients, whereas adult CD patients had upregulated levels of GM-CSF and IFN-γ. Taken together, these results demonstrate age-dependent differences in cytokine profiles, which may affect the pathogenesis of CD in patients at different ages of disease onset. PMID:28070144
Szabó, Dolóresz; Hosszú, Éva; Arató, András; Müller, Katalin Eszter; Béres, Nóra; Lakatos, Péter László; Papp, Mária; Dezsőfi, Antal; Szabó, Attila J; Szűcs, Dániel; Veres, Gabor
Paediatric Crohn's disease patients suffer from several complications, including low bone mineral density and inadequate serum levels of 25-hydroxy vitamin D. The aim of this prospective study was to address the effect of infliximab therapy on bone metabolism, bone mineral density and vitamin D homeostasis. The seasonal variability of serum vitamin D levels in relation to infliximab treatment was also analysed. Serum osteocalcin and beta-crosslaps (markers of bone metabolism), seasonal variability of vitamin D, and bone mineral density were assessed and followed throughout the yearlong treatment regimen of infliximab in 50 consecutive paediatric patients with moderate to severe Crohn's disease. Bone forming osteocalcin levels were significantly (p<0.001) increased during infliximab therapy. In contrast, no significant changes in beta-crosslaps and vitamin D levels were observed. Vitamin D levels were significantly different when the summer and winter periods were compared at week 0 (p=0.039); however, this difference was not detected after one year of infliximab therapy. Despite the beneficial clinical effect of infliximab, there was no significant change in bone mineral density Z-scores after one year of treatment. Infliximab may beneficially affect bone homeostasis. Moreover, seasonal variability in vitamin D levels observed prior to initiation of infliximab treatment was diminished after one year of treatment. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
González-Huix, F; de León, R; Fernández-Bañares, F; Esteve, M; Cabré, E; Acero, D; Abad-Lacruz, A; Figa, M; Guilera, M; Planas, R
Thirty two patients with active Crohn's disease were included in a controlled randomised trial to determine the efficacy and safety of polymeric enteral nutrition compared with steroids, to achieve and maintain clinical remission. The polymeric diet was administered through a fine bore nasogastric tube by continuous, pump assisted infusion (2800 (SEM 120) kcal/day). The steroid group received 1 mg/kg/day of prednisone. Both treatments were effective in inducing clinical remission: 15 of the 17 patients given steroids and 12 of the 15 patients assigned to the polymeric diet went into clinical remission (defined by a Van Hees index < 120) within four weeks of treatment. The percentage reduction of the Van Hees index was 34.8 (4.9)% for steroids and 32.3 (5)% for enteral nutrition (mean difference 2.5%; 95% CI--11.8% to +16.8%). Mean time elapsed to achieve remission was similar in both groups (2.0 (1) v 2.4 (1.2) weeks). Tolerance of the enteral diet was excellent. Four patients in the steroid group had mild complications attributable to this treatment. Ten patients (66.6%) in the steroid group and five (41.6%) in the enteral nutrition group relapsed within a year of discharge, but no differences were found in the cumulative probability of relapse during the follow up period. These results suggest that polymeric enteral nutrition is as safe and effective as steroids in inducing short term remission in active Crohn's disease. PMID:8314510
Fluxá, Daniela; Ibáñez, Patricio; Flores, Lilian; Figueroa, Carolina; Lubascher, Jaime; Kronberg, Udo; Simian, Daniela; Pizarro, Gonzalo; Toche, Paola; Quera, Rodrigo
Anti-tumor necrosis factor-α (TNF) agents have dramatically changed the management of Crohns Disease (CD). However, a significant number of these patients do not respond at all or cease to respond to antibodies against TNF. In this clinical situation, the options include intensification of anti-TNF therapy by either increasing the dose or by shortening the administration interval, the use of a second anti-TNF or medications with a different mechanism of action. Among the later, Natalizumab, a humanized IgG4 monoclonal antibody against α4β1 and α4β7 integrins, is safe and effective in inducing and maintaining remission in active CD patients refractory to anti-TNF. In spite of this, Natalizumab use has been limited because of an increased risk of progressive multifocal leukoencephalophaty which results from reactivation of the John Cunningham (JC) virus. However, the presence of antibodies against JC virus in serum can be used to reduce the risk for this complication. We report three patients with Crohns disease refractory to treatment with infliximab, who responded successfully to the use of Natalizumab.
Husain, Nisreen; Tokoro, Ken; Popov, Joanna M; Naides, Stanley J; Kwasny, Mary J; Buchman, Alan L
Neopterin, a pyrazino-[2,3-d]-pyrimidine compound, is a metabolite of cyclic guanosine monophosphate that is released by activated T lymphocytes and macrophages after induction by γ interferon. We sought to determine whether neopterin concentration in stool, serum, or urine is a useful marker of disease activity in patients with Crohn's disease or ulcerative colitis. We prospectively studied 70 outpatients (33 M, 37 F, aged 39.2 ± 14.0 y) with Crohn's disease (33 clinically in remission, 37 active), 52 outpatients (29 M, 23 F, aged 39.8 ± 12.2 y) with ulcerative colitis (29 clinically in remission, 23 active), and 141 healthy control subjects. Fecal, serum, and urine samples were analyzed for neopterin concentration and other analytes of interest. The following clinical indices were calculated at enrollment: for Crohn's disease, the Capetown Index and Harvey Bradshaw Index; for ulcerative colitis, Simple Clinical Colitis Activity Index, Disease Activity Index, and endoscopic disease severity (rated on a scale of 0 to 3). Crohn's disease was considered active if the Harvey Bradshaw Index was ≥ 5, and ulcerative colitis was considered active if the Simple Clinical Colitis Activity Index was >3. Among Crohn's disease patients, fecal neopterin was higher in those with either clinically active (96.0 ng/g) or inactive (87.2 ng/g) disease than in control subjects (12.0 ng/g; P<0.05; inactive or active disease vs. controls). For ulcerative colitis patients, fecal neopterin concentration was higher in those with active (135.2 ng/g) disease than in those with inactive disease (62.7 ng/g; P<0.05) or healthy controls (12.0 ng/g; P<0.05). Neither serum nor urine neopterin concentrations were increased in patients with active inflammatory bowel disease. Nonsignificant trends toward greater fecal neopterin concentration were observed with increased colonic disease involvement, although not with endoscopic severity or clinical disease activity indices. Fecal neopterin
Shin, In Seub; Seok, Hyeri; Eun, Yeong Hee; Lee, You-Bin; Lee, Seung-Eun; Kim, Eun Ran; Chang, Dong Kyung; Kim, Young-Ho
Micronutrient deficiencies in Crohn's disease (CD) patients are not uncommon and usually result in a combination of reduced dietary intake, disease-related malabsorption, and a catabolic state. Decreased serum thiamine levels are often reported in patients with CD. Wernicke's encephalopathy (WE) is a severe form of thiamine deficiency that can cause serious neurologic complications. Although WE is known to occur frequently in alcoholics, a number of non-alcoholic causes have also been reported. Here, we report two cases of non-alcoholic WE that developed in two severely malnourished CD patients who were supported by prolonged total parenteral nutrition without thiamine supplementation. These patients complained of sudden-onset ophthalmopathy, cerebellar dysfunction, and confusion. Magnetic resonance imaging allowed definitive diagnosis for WE despite poor sensitivity. The intravenous administration of thiamine alleviated the symptoms of WE dramatically. We emphasize the importance of thiamine supplementation for malnourished patients even if they are not alcoholics, especially in those with CD. PMID:27175122
Lake, A M; Kim, S; Mathis, R K; Walker, W A
The postoperative growth rates achieved in eight early pubertal adolescent males with Crohn's disease undergoing surgery for obstructive complications is reported as a function of the use of 1 month's preoperative central venous alimentation. All patients had ileal strictures with ileocolitis, bone ages less than 13, Tanner stages 1 or 2, and growth velocities below the 3rd percentile for age. During a 3-year follow-up, those receiving preoperative venous alimentation demonstrated greater oral caloric intake (significant for 1 year) and greater postoperative growth velocity (significant for 2 years) in comparison to those patients who did not receive preoperative venous alimentation. There was no significant difference between the two groups of patients in postoperative weight gain, sexual development, and 3-year disease control.
Niriella, Madunil A; Kodisinghe, S Kuleesha; De Silva, Arjuna P; Hewavisenthi, Janaki; de Silva, Hithanadura J
Crohn disease has low prevalence in Sri Lanka while compared to the West, while intestinal tuberculosis is common in the region. Since clinical, endoscopic and investigation features of Crohn disease overlap with intestinal tuberculosis, differentiating these two conditions becomes a dilemma for the clinician in the intestinal tuberculosis endemic setting. An 18-year old Sri Lankan Muslim female presented with chronic abdominal pain and weight loss. Colonoscopy revealed an ulcerated ileocaecal valve and a terminal ileal stricture. Biopsy confirmed Crohn disease with no supportive features to suggest intestinal tuberculosis. Despite treatment with adequate immunosuppression she failed to improve and underwent a limited right hemicolectomy and terminal ileal resection. Histology confirmed intestinal tuberculosis and she made full recover with 6 months of anti-tuberculosis treatment. This case illustrates the importance of reviewing the diagnosis to include intestinal tuberculosis in an endemic setting, when already diagnosed Crohn disease is treatment refractory.
Forni, E; Orlandoni, G; Voltolini, P; Zadra, F; Stradiotti, G; Bordoni, P; Spelzini, P
18 patients with Crohn's disease primarily treated with excisional surgery were studied. The crude recurrence and reoperation rate were analyzed. The influence of sex, age and length of history prior to operation was in this respect also studied.
Bartholo, R M; Zaltman, C; Elia, C; Cardoso, A P; Flores, V; Lago, P; Cassabian, L; Dorileo, F Carvalho; Lapa-e-Silva, J R
With the aim of investigating the presence of latent inflammatory process in the lungs of patients with Crohn's disease, 15 patients with Crohn's disease were evaluated by spirometry, the methacholine challenge test, induced sputum, and skin tests for inhaled antigens. Serum IgE, erythrocyte sedimentation rate and hematocrit were also determined. The patients were compared with 20 healthy controls by the Mann-Whitney and Fisher exact tests. Their respiratory physical examination was normal. None had a personal or family history of clinical atopy. None had a previous history of pulmonary disease, smoking or toxic bronchopulmonary exposure. None had sinusitis, migraine, diabetes mellitus, or cardiac failure. Four (26.6%) of the patients with Crohn's disease had a positive methacholine challenge test whereas none of the 20 controls had a positive methacholine test (P = 0.026, Fisher exact test). Patients with Crohn's disease had a higher level of lymphocytes in induced sputum than controls (mean 14.59%, range 3.2-50 vs 5.46%, 0-26.92%, respectively; P = 0.011, Mann-Whitney test). Patients with Crohn's disease and a positive methacholine challenge test had an even higher percentage of lymphocytes in induced sputum compared with patients with Crohn's disease and a negative methacholine test (mean 24.88%, range 12.87-50 vs 10.48%, 3.2-21.69%; P = 0.047, Mann-Whitney test). The simultaneous findings of bronchopulmonary lymphocytosis and bronchial hyperresponsiveness in patients with Crohn's disease were not reported up to now. These results suggest that patients with Crohn's disease present a subclinical inflammatory process despite the absence of pulmonary symptoms.
Uko, Victor; Vortia, Eugene; Achkar, Jean-Paul; Karakas, Pinar; Fiocchi, Claudio; Worley, Sarah; Kay, Marsha H
Increased abdominal visceral adipose tissue (VAT) is associated with systemic inflammation. The influence of VAT on pediatric inflammatory bowel disease (IBD) has not been studied. The objective of this study was to investigate the differences in VAT between pediatric patients with IBD and age-matched controls and identify associations between VAT and Crohn's disease (CD) outcomes. Single-center retrospective cohort study of 114 pediatric patients with IBD (101 CD and 13 ulcerative colitis) who had abdominal computed tomography at diagnosis. VAT volumes were measured from computed tomography images. A control group of 78 age-matched patients without IBD who had abdominal computed tomography was selected for comparison. Median VAT was 634 cm (interquartile range, 411-1041) in the IBD group and 659 cm (interquartile range, 394-1015) in the controls. IBD group had 33% higher VAT than controls (95% confidence interval [CI], 11-58) P = 0.002 after adjusting for body mass index and age. In patients with CD, higher VAT was associated with fistulizing or fibrostenotic disease (odds ratio [OR], 1.7; 95% CI, 1.1-2.9; P = 0.03), CD hospitalizations (OR, 1.9; 95% CI, 1.2-3.4; P = 0.01), moderate or severe disease activity scores (OR, 1.8; 95% CI, 1.1-3.1; P = 0.02), and shorter intervals from diagnosis to surgery (hazard ratio, 1.4; 95% CI, 1.0-2.0; P = 0.05) after adjusting for body mass index and age. At diagnosis, pediatric patients with IBD have higher adjusted VAT volumes than age- and body mass index-matched controls. Higher VAT volumes in pediatric patients with CD predicted more hospitalizations, increased likelihood of complicated disease, shorter interval from diagnosis to surgery, and higher disease activity scores at diagnosis.
DiNicola, C A; Zand, A; Hommes, D W
Autologous hematopoietic stem cells are gaining ground as an effective and safe treatment for treating severe refractory Crohn's disease (CD). Autologous hematopoietic stem cell therapy (AHSCT) induces resetting of the immune system by de novo regeneration of T-cell repertoire and repopulation of epithelial cells by bone-marrow derived cells to help patients achieve clinical and endoscopic remission. Areas covered: Herein, the authors discuss the use of AHSCT in treating patients with CD. Improvements in disease activity have been seen in patients with severe autoimmune disease and patients with severe CD who underwent AHSCT for a concomitant malignant hematological disease. Clinical and endoscopic remission has been achieved in patients treated with AHSCT for CD. The only randomized trial published to date, the ASTIC Trial, did not support further use of AHSCT to treat CD. Yet, critics of this trial have deemed AHSCT as a promising treatment for severe refractory CD. Expert opinion: Even with the promising evidence presented for HSCT for refractory CD, protocols need to be refined through the collaboration of GI and hemato-oncology professionals. The goal is to incorporate safe AHSCT and restore tolerance by delivering an effective immune 'cease fire' as a treatment option for severe refractory CD.
Bauditz, J; Haemling, J; Ortner, M; Lochs, H; Raedler, A; Schreiber, S
BACKGROUND: In Crohn's disease, inflammation is presumably sustained by an increased production of proinflammatory cytokines, in particular tumour necrosis factor alpha (TNF alpha) and interleukin 1 beta (IL 1 beta). TNF alpha can induce a host of cellular effector events resulting in perpetuation of the inflammatory process. In vivo studies with anti-TNF alpha antibody treatment have led to impressive clinical results. AIMS: To investigate whether treatment with the TNF alpha inhibitor oxpentifylline results in clinical improvement in corticosteroid dependent chronic active Crohn's disease. METHODS: Sixteen Crohn's disease patients received oxpentifylline 400 mg four times a day in a four week open label study. RESULTS: Blockade of TNF alpha production in 16 patients with corticosteroid dependent Crohn's disease did not improve the clinical disease activity (CDAI mean (SEM) 188.75 (5.65) versus 185.13 (10.87) or the endoscopic degree of inflammation (CDEIS 14.9 (2.87) versus 14.8 (2.27) or laboratory parameters. CONCLUSIONS: In this study, use of the TNF alpha inhibitor oxpentifylline does not improve inflammation in Crohn's disease. This finding suggests that there may be more key mediators than only TNF alpha in the inflammatory process in Crohn's disease. PMID:9176073
Subramanian, Sreedhar; Ekbom, Anders; Rhodes, Jonathan M
The genetics of isolated colonic Crohn's disease place it approximately midway between Crohn's disease with small intestinal involvement and UC, making a case for considering it as a separate condition. We have therefore systematically reviewed its epidemiology, pathophysiology and treatment. Key findings include a higher incidence in females (65%) and older average age at presentation than Crohn's disease at other sites, a mucosa-associated microbiota between that found in ileal Crohn's disease and UC, no response to mesalazine, but possibly better response to antitumour necrosis factor than Crohn's disease at other sites. Diagnostic distinction from UC is often difficult and also needs to exclude other conditions including ischaemic colitis, segmental colitis associated with diverticular disease and tuberculosis. Future studies, particularly clinical trials, but also historical cohorts, should assess isolated colonic Crohn's disease separately. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Gibson, P R; Shepherd, S J
Susceptibility to the development of Crohn's disease involves a combination of genetic and environmental factors. The association of Crohn's disease with westernization has implicated lifestyle factors in pathogenesis. While diet is a likely candidate, evidence for specific changes in dietary habits and/or intake has been lacking. A new hypothesis is proposed, by which excessive delivery of highly fermentable but poorly absorbed short-chain carbohydrates and polyols (designated FODMAPs--Fermentable Oligo-, Di- and Mono-saccharides And Polyols) to the distal small intestinal and colonic lumen is a dietary factor underlying susceptibility to Crohn's disease. The subsequent rapid fermentation of FODMAPs in the distal small and proximal large intestine induces conditions in the bowel that lead to increased intestinal permeability, a predisposing factor to the development of Crohn's disease. Evidence supporting this hypothesis includes the increasing intake of FODMAPs in western societies, the association of increased intake of sugars in the development of Crohn's disease, and the previously documented effects of the ingestion of excessive FODMAPs on the bowel. This hypothesis provides potential for the design of preventive strategies and raises concern about current enthusiasm for putative health-promoting effects of FODMAPs. One of the greatest challenges in defining the pathogenesis of Crohn's disease is to identify predisposing environmental factors. Such an achievement might lead to the development of preventive strategies for, and the definition of, possible target for changing the natural history of this serious disease. The present paper describes a new hypothesis for one such environmental factor.
Gale, G; Östman, S; Rekabdar, E; Torinsson Naluai, Å; Högkil, K; Hasséus, B; Saalman, R; Jontell, M
To compare oral manifestations in a Swedish cohort of patients with orofacial granulomatosis with or without Crohn's disease and to assess NOD2 polymorphisms in the two groups. Twenty-nine patients with orofacial granulomatosis were included. Demographics, disease history, clinical features and concurrent Crohn's disease were recorded. DNA was extracted from buccal swabs and examined for NOD2 variants Arg702Trp, Gly908Arg and Leu1007fsinsC, all previously linked to gastrointestinal Crohn's disease. Twelve of 29 patients were diagnosed with coexisting gastrointestinal Crohn's disease, and of whom 21 were males. Symptom duration was significantly longer for the orofacial granulomatosis group com-pared to the group with coexisting Crohn's disease (P < 0.0001). The orofacial granulomatosis patients also perceived their overall discomfort, aesthetic problems and social discomfort as more severe. No significant differences in the clinical presentation of oral lesions between the two groups were found. None of the patients with orofacial granulomatosis carried any of the NOD2 variations, whereas four of the 12 patients with coexisting Crohn's disease had a NOD2 variant (Arg702Trp). The two patient groups had similar phenotypic characteristics but seemed to have genotypic differences regarding NOD2. The Swedish cohort differed in their clinical characteristics from patients reported in other geographical regions. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Colombel, J F; Guillemot, F; Van Gossum, A; Dufossé, F; Cortot, A; Dupont, E; Paris, J C
We report five families with 3 or more children having Crohn's disease. In one family, 6 out of 11 siblings were affected. HLA haplotype study in affected children showed that the probability of random segregation was only 38 percent, making improbable a linkage between the histocompatibility locus and the development of Crohn's disease. However similar clinical patterns in siblings could suggest a genetic factor not linked to the HLA system.
Tamzaourte, Mouna; Errabih, Ikram; Krami, Hayat; Maha, Fadlouallah; Maria, Lahmiri; Benzzoubeir, Nadia; Ouazzani, Laaziza; Sefiani, Ahmed; Ouazzani, Houria
The aim of this study was to determine the prevalence of NOD2/CARD15 gene mutations in a group of Moroccan patients with Crohn's disease and to study its correlation with genotype-phenotypic expression. We conducted a cross-sectional case-control study over a period of 16 months. 101 patients with Crohn's disease were enrolled between January 2012 and April 2013 as well as a control group of 107 patients. We performed a genetic analysis to identify 3 NOD2 gene variants: p.Arg702Trp, p.Gly908Arg and p.Leu1007fsins. Then we conducted a study of the correlation between genotype and phenotypic expression. The genetic analysis of patients with Crohn's disease highlighted the presence of NOD2 mutation in 14 patients (13.77%) versus 7 patients (6.53%) in the control group. The study of the frequency of different alleles showed p.Gly908Arg mutation in 6.43%, p.Leu1007fsins in 0.99% and p.Arg702Trp in 0.49% versus 2.80%, 0% and 0.46% in the control group respectively. The study of the correlation between genotype and phenotypic expression showed that CARD15 mutation is associated with ileocecal Crohn's disease, with fistulizing and stenosing behavior in Crohn's disease as well as with severe evolution and frequent recourse to surgery and immunosuppressants. The prevalence of NOD2/ CARD15 mutation in our case series is low. This mutation is correlated with severe Crohn's disease.
Araki, Toshimitsu; Okita, Yoshiki; Fujikawa, Hiroyuki; Ohi, Masaki; Tanaka, Koji; Inoue, Yasuhiro; Uchida, Keiichi; Mohri, Yasuhiko; Kusunoki, Masato
Pouch failure has been reported to occur after ileal pouch-anal anastomosis for Crohn's disease. We report two cases of patients with Crohn's disease, who underwent redo ileal pouch-anal anastomosis (redo-IPAA) combined with anti-TNF-α maintenance therapy, with good functional results. The first patient, a man with presumed ulcerative colitis, suffered pelvic fistula recurrence and anastomotic dehiscence. He underwent redo-IPAA, at which time longitudinal ulcers were found. Infliximab was started 4 days postoperatively and continued. The second patient, a woman treated for ulcerative colitis, underwent laparoscopic IPAA 8 years later. After the development of a pelvic fistula, twisted mesentery of the ileal pouch was found intraoperatively and Crohn's disease was diagnosed. Adalimumab therapy resulted in fistula closure. Redo-IPAA was performed to normalize the twisted mesentery of the ileal pouch. No complications have been observed in either patient, both of whom have experienced good functional results after closure of the covering stomas.
Gu, Jinyu; Stocchi, Luca; Kiran, Ravi P; Shen, Bo; Remzi, Feza H
Data on the association between ileal pouch retention and clinical characteristics of pouch Crohn's disease developing after restorative proctocolectomy for ulcerative colitis are still limited. The aim of this study was to identify whether clinical features of pouch Crohn's disease are associated with pouch retention. The study was conducted in a tertiary referral center. All patients diagnosed with clinically active pouch Crohn's disease during follow-up after IPAA for ulcerative colitis or indeterminate colitis were identified from an ileal pouch registry. The definition of early vs late diagnosis was based on the median time interval to diagnosis of Crohn's disease after pouch creation. The associations between pouch retention and the clinical features and treatments of pouch Crohn's disease were analyzed. The long-term pouch retention rate was estimated by using the Kaplan-Meier method. Multivariate logistic regression was used to analyze independent factors for pouch failure. From 1993 to 2009, a total of 65 (28 males) patients developed de novo pouch Crohn's disease during a mean 7.9 years of follow-up after pouch creation. The overall pouch retention rate was 57%. The median time from pouch creation to pouch Crohn's disease diagnosis was 3.6 years. Univariate analysis demonstrated that early diagnosis of pouch Crohn's disease, disease location, and clinical manifestations at the time of diagnosis were associated with pouch outcomes, whereas medical therapy or perianal surgery was not. Multivariate analysis showed that fistula at the time of diagnosis (OR = 17.5, p = 0.002) and early diagnosis (OR = 5.70, p = 0.011) were independent risk factors for pouch failure, whereas afferent limb disease was associated with pouch retention (OR = 0.07, p = 0.018). The retrospective nature of this study and referral bias were limitations. Disease characteristics of de novo pouch Crohn's disease heavily influence pouch retention. The interval from pouch construction
Alessandroni, L; Kohn, A; Cosintino, R; Marrollo, M; Papi, C; Monterubbianesi, R; Tersigni, R
Perianal fistulas are frequent complications of Crohn's disease. Intravenous infliximab can control perianal disease and promote perianal fistula closure. Perifistular infliximab injections have been proposed for patients who are intolerant or unresponsive to intravenous therapy. The aim of this study was to assess the long-term efficacy of surgical treatment combined with local infliximab therapy. A prospective cohort study was designed. Twelve patients with Crohn's disease and high/complex transphincteric and intrasphincteric perianal fistulas refractory to other treatment were submitted to core-out fistulectomies, plus perifistular injections of infliximab (20-25 mg in 15-20 ml of 5% glucose) every 4-6 weeks. The main outcome measure was the clinical closure of all perianal fistulas. A 95% confidence interval was calculated for short- and long-term fistula closure rates. None of the procedures were associated with local or systemic adverse effects. Four patients did not complete treatment, two because of relapse of intestinal symptoms, which required intravenous infliximab. In one case, treatment with intravenous infliximab was complicated by a hypersensitivity reaction. Eight patients continued treatment until all perianal fistulas were closed and setons were removed (median: 5 sessions). Persistent closure was observed in seven (87.5%, 95% CI: 47.4-99.6) of the eight patients 12 months after completion of treatment and in five (62.5%; 95% CI: 24.5-91.5) of eight at the end of follow-up (range: 19-43 months, median: 35 months). The cohort we examined is small, but fistulectomy combined with repeated perifistular injections of infliximab appears to be safe and may help in fistula healing. However, in most patients, permanent closure of all fistulas is not achieved.
Amarapurkar, D N; Patel, N D; Amarapurkar, A D; Agal, S; Baigal, R; Gupte, P
1) To evaluate the utility of PCR in differentiating intestinal tuberculosis from Crohn's disease. 2) To compare histological features of tuberculosis and Crohn's disease. A total of 60 cases of diagnosed intestinal tuberculosis and 20 Crohn's disease were included in the study. Clinical data, radiological and endoscopic findings and response to treatment were taken into consideration. Endoscopic biopsies from affected areas were subjected to histopathological examination and polymerase chain reaction (PCR) assay. Acid fast staining on tissue and culture was done whenever possible. Clinical symptoms, radiological and endoscopic findings were almost similar between intestinal tuberculosis and Crohn's disease. PCR was positive in 21.6% cases of intestinal tuberculosis and 5% Crohn's disease. Nine out of 42 cases (21.4%) without granuloma were also positive by PCR. There was no statistical difference for PCR positivity between patients with intestinal tuberculosis with or without granuloma on histology and also between caseating and non-caseating granuloma. PCR assay showed high specificity (95%) for the diagnosis of intestinal tuberculosis hence may be valuable method to differentiate intestinal tuberculosis from Crohn's disease.
Lian, Yanbang; Cao, Wuteng; Zhu, Shanshan; Lin, Yanghao; Liu, Dechao; Wang, Xinhua; Qiu, Jianping; Zhou, Zhiyang
To evaluate the application of low-dose CT enterography with adaptive iterative dose reduction(AIDR) technique in diagnosing Crohn's disease. Retrospective analysis was performed on 26 patients diagnosed as Crohn's disease by the multidisciplinary team in our hospital. Low-dose CT enterography with 640-slice MDCT was performed on these 26 patients using adaptive iterative dose reduction(AIDR) technique. Characteristics of Crohn's disease in CT enterography images were independently analyzed by two radiologists who were experienced in Crohn's disease with calculating the total radiation dosage. The radiation dosage of 26 patients ranged from 5.58 to 12.90 [mean (9.00±2.00)] mSv, which was lower than conventional scan (around 15 mSv) known from the literatures. According to the images of CT enterography of 26 cases, bowel wall thickening with abnormal enhancement and lymphadenectasis were found in 25 cases with total 109 segmental bowel wall thickening. Among 25 thickening cases, enterostenosis was found in 16 cases, stratification enhancement in 12 cases and comb sign in 14 cases. Besides, it was found that 8 cases with hyperdense fat on the mesenteric side, 7 cases with intestinal fistula, 6 cases with abdominal cavity abscess, and 3 cases with anal fistula. CT enterography of Crohn's disease with adaptive iterative dose reduction technique is an effective method to evaluate Crohn's disease without compromising image quality with reduced radiation dosage.
Tseng, Chia-Chun; Yen, Jeng-Hsien; Tsai, Wen-Chan; Ou, Tsan-Teng; Wu, Cheng-Chin; Sung, Wan-Yu; Hsieh, Ming-Chia; Chang, Shun-Jen
To date, there has been no studies to evaluate the incidence of Crohn's disease in systemic sclerosis patients. The goals of this study were to evaluate the incidence of Crohn's disease and its relationship with sex and age in patients with systemic sclerosis. We enrolled patients with systemic sclerosis and controls from Taiwan's Registry of Catastrophic Illness Database and National Health Insurance Research Database. Every systemic sclerosis patient was matched to at most three controls by sex, age, month and year of initial diagnosis of systemic sclerosis. The standardized incidence ratio (SIR) of Crohn's disease in systemic sclerosis patients, and 95% confidence interval (95% CI) were calculated. Cox hazard regression was used to calculate the hazard ratio (HR). The study enrolled 2,829 patients with systemic sclerosis and 8,257 controls. Male and female patients with systemic sclerosis both had lower rates of incident Crohn's disease (SIR: 0.18, 95% CI = 0.05-0.62; SIR: 0.10, 95% CI = 0.05-0.21, respectively). The risk of incident Crohn's disease in systemic sclerosis was still lower than in controls when we stratified the patients according to their ages. In Cox hazard regression, the hazard rates of Crohn's disease were lower in systemic sclerosis patients after adjusting for genders and ages (HR: 0.12, 95% CI = 0.06-0.21, p < 0.001). Systemic sclerosis is associated with decreased incidence of, irrespective of sex and age of the patients.
Shimizu, T; Nishinarita, S; Son, K; Tomita, Y; Yoshihiro; Matsukawa; Kitamura, N; Horie, T; Baba, M; Hiranuma, M
We described a 37-year-old man with Crohn's disease (CD) resembling systemic lupus erythematosus (SLE) at his disease onset. He was admitted to the municiple Akiru Hospital in October 1986 by fever, aphtous oral ulcerations, sore throat and polyarthralgia. Hematologic examination showed leukocytopenia, lymphocytopenia, positive tests for antinuclear antibody, anti-DNA antibody and LE cell phenomenon. He has had episodes of convulsion and conciousness loss of unknown etiology when he was 17 years old. The diagnosis of SLE was made, and oral medication of prednisolone was started. Several weeks later, most of symptoms and autoantibodies disappeared, although the oral aphtous ulcerations and leukocytopenia remained. In May 1987, he admitted to the other hospital because of bloody vomiting. Endoscopic examination showed the esophagial ulceration, and histology of biopsied-specimen was nonspecific esophagitis. The combination of prednisolone and oral cyclophosphamide or methotrexate was employed thereafter. However, the leukocytopenia, oral aphtous ulceration and esophagial ulceration continued in spite of these treatments. All the immunosuppressive treatment was stopped at March 1992. In October 1995, he admitted to our hospital because of body weight loss and continuous diarrhea with occasional bloody stool. Barium enema and endoscopic examination of the colon revealed the findings compatible with CD. The patient responded favorably to methylprednisolone pulse therapy followed by oral sulphasalazine. This case indicated that cases with inflammatory bowel diseases like CD could show similar clinical signs and symptoms to SLE, and in some cases of CD might satisfied the classification of criteria for SLE.
Gupta, Neera; Bostrom, Alan G; Kirschner, Barbara S; Ferry, George D; Winter, Harland S; Baldassano, Robert N; Gold, Benjamin D; Abramson, Oren; Smith, Terry; Cohen, Stanley A; Heyman, Melvin B
The objective of this study was to determine gender differences in pediatric patients with Crohn disease. We conducted a retrospective cohort study of 989 consecutive pediatric patients (566 boys, 423 girls) who had Crohn disease (aged 0 to 17 years at diagnosis) by using the Pediatric IBD Consortium Registry. Uniform data were analyzed to compare the presentation and course of disease according to gender. Median follow-up time was 2.8 years. Mean +/- SD age at diagnosis of inflammatory bowel disease (11.5 +/- 3.8 years) did not differ by gender. Compared with boys, girls had a higher prevalence of mouth sores at symptom onset and a higher prevalence of hypoalbuminemia at the time of diagnosis. Location of disease did not differ by gender. A higher proportion of girls had abnormal anti-outer membrane porin of Escherichia coli levels compared with boys. Girls were at increased risk for erythema nodosum/pyoderma gangrenosum and decreased risk for growth failure compared with boys. Girls appear to have an overall more severe course of disease; however, boys are at increased risk for developing growth failure. Disease course and the impact of disease severity on growth according to gender in pediatric Crohn disease require prospective study.
Brookes, Matthew J; Green, Jonathon R B
Crohn's disease is a chronic inflammatory bowel disorder with a relapsing and remitting course. Once remission is achieved, the main aim of the management of Crohn's disease is maintenance of that remission. Significant advances have been made into understanding the aetiology and pathogenesis of inflammatory bowel disease. With these advances in understanding come increasing numbers of new agents and therapies, aimed both at active disease and the subsequent maintenance of remission in Crohn's disease. Current therapeutic strategies in maintaining remission in Crohn's disease include 5-aminosalicylates (e.g. sulfasalazine, mesalazine), thiopurines (e.g. azathioprine, 6-mercaptopurine [mercaptopurine]), methotrexate and infliximab. The 5-aminosalicylates appear to have efficacy limited to either surgically induced remission and/or limited small bowel Crohn's disease. The immunomodulators now have an established role in Crohn's maintenance. Azathioprine and 6-mercaptopurine are effective in chronic active disease and corticosteroid-dependent Crohn's disease. Methotrexate has similar indications, although it appears to be an alternative in patients who are intolerant of, or resistant to, the thiopurines. The most recent breakthrough has been in the field of biological therapy for maintenance of remission in Crohn's disease. Treatment of patients with the anti-tumour necrosis factor (TNF)-alpha antibody infliximab has been shown already to be effective in inducing remission. Recent studies have now confirmed a role for infliximab in delaying relapse and maintaining remission in patients responsive to infliximab induction therapy. However, results with soluble TNF alpha receptors have been disappointing. A number of other biological and nonbiological agents have shown potential, though trials of the 'newer' biological agents have thus far been disappointing, in the maintenance of remission in Crohn's disease. The evidence for theses agents is currently limited, in many
Hartley, J E; Fazio, V W; Remzi, F H; Lavery, I C; Church, J M; Strong, S A; Hull, T L; Senagore, A J; Delaney, C P
Ileal pouch-anal anastomosis has come to represent the procedure of choice for patients requiring surgery for mucosal ulcerative colitis. In contrast, a proven diagnosis of Crohn's disease is generally held to preclude ileal pouch-anal anastomosis. However, patients with ileal pouch-anal anastomosis for apparent mucosal ulcerative colitis who are subsequently found to have Crohn's disease have a variable course. We reviewed our experience in this scenario to determine whether selected patients with Crohn's disease may be candidates for ileal pouch-anal anastomosis. A retrospective review of the prospectively maintained ileal pouch-anal anastomosis database was undertaken to identify patients with a diagnosis of Crohn's disease after ileal pouch-anal anastomosis. Clinical outcome and quality-of-life data were obtained from the database and chart review. End points were the development of recrudescent Crohn's disease, pouch failure, and quality of life and functional outcome at the time of data collection. Differences between groups were calculated using the chi-squared test. Cumulative incidence of recrudescent Crohn's disease and pouch loss were calculated by the Kaplan-Meier method. Factors predictive of development of recrudescent Crohn's disease and pouch loss were examined by univariate analysis. Sixty patients (32 females; median age, 33 (range, 15-74) years) who underwent ileal pouch-anal anastomosis for mucosal ulcerative colitis subsequently had that diagnosis revised to Crohn's disease. Median follow-up of all patients was 46 (range, 4-158) months at time of data collection by which time 21 patients (35 percent) had developed recrudescent Crohn's disease. No pre-ileal pouch-anal anastomosis factors examined were predictors of the development of recrudescent Crohn's disease on univariate analysis. Median follow-up of the latter group was 63 (range, 0-132) months from time of diagnosis, by which time six patients underwent pouch excision and another patient
O'Neill, Siobhan B; Mc Laughlin, Patrick D; Crush, Lee; O'Connor, Owen J; Mc Williams, Sebastian R; Craig, Orla; Mc Garrigle, Anne Marie; O'Neill, Fiona; Bye, Jackie; Ryan, Max F; Shanahan, Fergus; Maher, Michael M
Iterative reconstruction (IR) allows diagnostic CT imaging with less radiation exposure than filtered back projection (FBP). We studied an IR low-dose CT abdomen/pelvis (LDCTAP) protocol, designed to image at an effective dose (ED) approximating 1 mSv in patients with Crohn's disease (CD). Forty patients, mean age 37 ± 13.4 years (range 17-69), with CD underwent two synchronous CT protocols (conventional-dose (CDCTAP) and LDCTAP). CDCTAP and LDCTAP images were compared for diagnostic acceptability, yield, image quality and ED (in millisieverts). The optimal level of IR for LDCTAP was also studied. LDCTAP yielded a mean ED of 1.3 ± 0.8 mSv compared with 4.7 ± 2.9 mSv for CDCTAP, reducing ED by 73.7 ± 3.3 % (mean dose reduction, 3.5 ± 2.1 mSv; P < 0.001) and dose length product by 73.6 ± 2.6 % (P < 0.001). Sub-millisievert (0.84 mSv) imaging was performed for patients with a body mass index (BMI) less than 25 (i.e. 63 % of our cohort). LDCTAP resulted in increased image noise and reduced diagnostic acceptability compared with CDCTAP despite use of IR, but detection of extra-luminal complications was comparable. Patients with suspected active CD can be adequately imaged using LDCTAP, yielding comparable information regarding extent, activity and complications of CD compared with CDCTAP, but with 74 % less dose. LDCTAP at doses equivalent to that of two abdominal radiographs represents a feasible alternative to CDCTAP. • Radiation dose is a concern when imaging patients with Crohn's disease. • New techniques allow low-dose abdominopelvic CT with acceptable image quality. • Using hybrid iterative reconstruction, its diagnostic yield compares well with that of conventional CT. • Sub-millisievert CT of patients with Crohn's disease appears technically and clinically feasible.
Jansen, Irene; Prager, Matthias; Valentini, Luzia; Büning, Carsten
Malnutrition is a frequent feature in Crohn's disease (CD), affects patient outcome and must be recognised. For chronic inflammatory diseases, recent guidelines recommend the development of combined malnutrition and inflammation risk scores. We aimed to design and evaluate a new screening tool that combines both malnutrition and inflammation parameters that might help predict clinical outcome. In a prospective cohort study, we examined fifty-five patients with CD in remission (Crohn's disease activity index (CDAI) <200) at 0 and 6 months. We assessed disease activity (CDAI, Harvey-Bradshaw index), inflammation (C-reactive protein (CRP), faecal calprotectin (FC)), malnutrition (BMI, subjective global assessment (SGA), serum albumin, handgrip strength), body composition (bioelectrical impedance analysis) and administered the newly developed 'Malnutrition Inflammation Risk Tool' (MIRT; containing BMI, unintentional weight loss over 3 months and CRP). All parameters were evaluated regarding their ability to predict disease outcome prospectively at 6 months. At baseline, more than one-third of patients showed elevated inflammatory markers despite clinical remission (36·4 % CRP ≥5 mg/l, 41·5 % FC ≥100 µg/g). Prevalence of malnutrition at baseline according to BMI, SGA and serum albumin was 2-16 %. At 6 months, MIRT significantly predicted outcome in numerous nutritional and clinical parameters (SGA, CD-related flares, hospitalisations and surgeries). In contrast, SGA, handgrip strength, BMI, albumin and body composition had no influence on the clinical course. The newly developed MIRT was found to reliably predict clinical outcome in CD patients. This screening tool might be used to facilitate clinical decision making, including treatment of both inflammation and malnutrition in order to prevent complications.
Ognibene, Noemi Maria Giovanna; Basile, Massimo; Di Maurizio, Marco; Petrillo, Giuseppe; De Filippi, Claudio
The aim of this paper is to provide indications for performing magnetic resonance enterography (MRE) in Crohn's disease (CD), the essential technical elements of MRE techniques and typical findings in patients with CD. Patients suffering from CD frequently require cross-sectional imaging. By performing MRE, it is possible to obtain results comparable to those obtained with endoscopy in terms of identifying and assessing disease activity and better than other cross-sectional imaging techniques, such as CT, in the evaluation of the fibrosis and complications of disease. The MR imaging of diffusion MR is a technique which enables medical staff to add important additional information and which may replace the use of intravenous contrast agents in the near future. Magnetic resonance enterography is an accurate tool for assessing bowel disease and the various complications associated with CD. The lack of exposure to non-ionizing radiation is an important advantage of this imaging technique, especially in the case of pediatric patients. Familiarity with common and pathognomonic imaging features of CD is essential for every clinician involved in the treatment of inflammatory bowel disease and the care of patients.
Reitsma, W; Wiegman, M J; Damstra, R J
Crohn's disease is an inflammatory intestinal disease that primarily causes abdominal pain and diarrhea. We report a male patient who presented with penile and scrotal lymphedema and inguinal fistulas as the first manifestations of Crohn's disease. Extraintestinal or metastatic Crohn's disease initially presenting as genital lymphedema with fistula formation is rare. Skin lesions in extraintestinal Crohn's disease typically show non-caseating, sarcoidal granulomas with numerous foreign body- and Langhans-type multinucleated giant cells, which are separated from intestinal involvement by normal skin. Treatment options are limited and include multi-immunosuppressant medications.
Li Yim, Andrew Y F; Duijvis, Nicolette W; Zhao, Jing; de Jonge, Wouter J; D'Haens, Geert R A M; Mannens, Marcel M A M; Mul, Adri N P M; Te Velde, Anje A; Henneman, Peter
Crohn's disease (CD) is a chronic inflammatory disorder belonging to the inflammatory bowel diseases (IBD). CD affects distinct parts of the gastrointestinal tract, leading to symptoms including diarrhea, fever, abdominal pain, weight loss, and anemia. The aim of this study was to assess whether the DNA methylome of peripheral blood cells can be associated with CD in women. Samples were obtained from 18 female patients with histologically confirmed ileal or ileocolic CD and 25 healthy age- and gender-matched controls (mean age and standard deviation: 30.5 ± 6.5 years for both groups). Genome-wide DNA methylation was determined using the Illumina HumanMethylation 450k BeadChip. Our analysis implicated 4287 differentially methylated positions (DMPs; corrected p < 0.05) that are associated to 2715 unique genes. Gene ontology enrichment analysis revealed significant enrichment of our DMPs in immune response processes and inflammatory pathways. Of the 4287 DMPs, 32 DMPs were located on chromosome X with several hits for MIR223 and PABPC5. Comparison with previously performed (epi)genome-wide studies revealed that we replicated 33 IBD-associated genes. In addition to DMPs, we found eight differentially methylated regions (DMRs). CD patients display a characteristic DNA methylation landscape, with the differentially methylated genes being implicated in immune response. Additionally, DMPs were found on chromosome X suggesting X-linked manifestations of CD that could be associated with female-specific symptoms.
Wei, Jiang-Peng; Wu, Xiao-Yan; Gao, Sen-Yang; Chen, Qiu-Yu; Liu, Tong; Liu, Gang
Abstract The differential diagnosis of Crohn's disease (CD) and intestinal tuberculosis (ITB) remains difficult as the clinical symptoms of the 2 digestive diseases are so similar. Here we report a case where a patient was initially misdiagnosed with ITB prior to the correct CD diagnosis. The 46-year-old male patient was hospitalized elsewhere for pain in the right lower abdomen and underwent an appendectomy. The pathological diagnosis was ITB and the patient was administered antituberculosis therapy for 1 year. Afterward, the patient was readmitted to the hospital for a right lower abdominal mass. A computed tomography scan revealed intestinal gas, fistula, and abdominal mass. We performed a right hemicolectomy on the patient. Postoperatively, we diagnosed the patient with CD, based on patient history and pathological examination. According to the CD active index (CDAI), the patient was at high risk and began treatment with infliximab. The patient has remained in complete remission and made a good recovery after 8-months follow-up. We compared this case with the results of a literature review on the misdiagnosis between CD and ITB (26 previously reported cases) to determine the characteristics of misdiagnosed cases. We found that distinguishing between ITB and CD is difficult because of their varied clinical presentation, nonspecific investigative tools, and profound similarities even in pathological specimens. Although a CT scan to determine the morphology of the bowel wall is a key for correct diagnosis, each case still poses challenges for diagnosis and administrating the appropriate treatment. PMID:26735549
Coretti, Lorena; Natale, Alessandro; Cuomo, Mariella; Florio, Ermanno; Keller, Simona
Crohn's disease (CD) is a chronic inflammation of the intestinal mucosa, characterized by periods of acute recurrence and remission. Depending on the specific region affected, CD is classified as ileal CD or colonic CD. It is largely accepted that the intestinal microbiota is involved in the onset of the pathology. Indeed, a reduced immune tolerance to components of the intestinal commensal microbiota and inflammation of the intestinal barrier typifies patients with CD. Several studies have shown defective expression of intestinal antimicrobial peptides (AMPs) in patients with CD compared to controls, particularly defensins. A reduction in α-defensins is observed in ileal CD, while β-defensins are increased in colonic CD. In addition to an immunological basis, the disease is frequently associated with genetic alterations including mutations of NOD2 gene. Several therapeutic strategies to circumvent the dysfunction observed in CD are currently under investigation. These include the use of delivery systems to administer endogenous AMPs and the engineering of peptidomimetics that could ameliorate the severity of CD. In this review, the role defensins play in CD and the strategies aimed at overcoming bacterial resistance will be discussed. PMID:28246439
Kim, Jihye; Park, Jae Yong; Hong, Seung Wook; Lee, Joo Young; Kang, Jin Woo; Hwang, Seongjun; Ko, Sang-Bae; Im, Jong Pil; Kim, Joo Sung
Metronidazole is a widely used antibiotic for the treatment of anaerobic bacterial infections. Metronidazole-induced encephalopathy (MIEP) is a rare but potentially reversible disease. The mechanism of MIEP remains unclear, and differences in the neurotoxic effects of oral versus intravenous (IV) metronidazole administration have not yet been determined. We report the case of a Crohn's disease (CD) patient who experienced encephalopathy immediately after a single IV dose of metronidazole following long-term exposure to the oral form of the drug. The 64-year-old man with intractable CD experienced a sudden change in mental status, aphasia, and muscle weakness after IV administration of metronidazole. He had previously taken metronidazole orally for 13 years and received intermittent IV metronidazole treatments for CD exacerbation. Brain magnetic resonance imaging (MRI) showed high-intensity signals in the bilateral medial thalamus and the midbrain and pontine tegmentum on fluid-attenuated inversion recovery images. After discontinuation of metronidazole, the high-intensity brain MRI signals resolved and the patient's mental status dramatically improved; however, the patient exhibited mild cognitive dysfunction 2 months after the onset of encephalopathy. PMID:28239323
Wright, Emily K; Kamm, Michael A; Dr Cruz, Peter; Hamilton, Amy L; Ritchie, Kathryn J; Bell, Sally J; Brown, Steven J; Connell, William R; Desmond, Paul V; Liew, Danny
To define the cost-effectiveness of strategies, including endoscopy and immunosuppression, to prevent endoscopic recurrence of Crohn's disease following intestinal resection. In the "POCER" study patients undergoing intestinal resection were treated with post-operative drug therapy. Two thirds were randomized to active care (6 mo colonoscopy and drug intensification for endoscopic recurrence) and one third to drug therapy without early endoscopy. Colonoscopy at 18 mo and faecal calprotectin (FC) measurement were used to assess disease recurrence. Administrative data, chart review and patient questionnaires were collected prospectively over 18 mo. Sixty patients (active care n = 43, standard care n = 17) were included from one health service. Median total health care cost was $6440 per patient. Active care cost $4824 more than standard care over 18 mo. Medication accounted for 78% of total cost, of which 90% was for adalimumab. Median health care cost was higher for those with endoscopic recurrence compared to those in remission [$26347 (IQR 25045-27485) vs $2729 (IQR 1182-5215), P < 0.001]. FC to select patients for colonoscopy could reduce cost by $1010 per patient over 18 mo. Active care was associated with 18% decreased endoscopic recurrence, costing $861 for each recurrence prevented. Post-operative management strategies are associated with high cost, primarily medication related. Calprotectin use reduces costs. The long term cost-benefit of these strategies remains to be evaluated.
Opstelten, Jorrit L.; Plassais, Jonathan; van Mil, Saskia W. C.; Achouri, Emna; Pichaud, Matthieu; Siersema, Peter D.; Cervino, Alessandra C. L.
Background: Smoking has a negative impact on Crohn's disease (CD), but the mechanisms underlying this association are unclear. We compared the gut microbiota composition of smoking with nonsmoking patients with CD using a metagenomic approach. Methods: Stool samples and clinical data were collected from current smokers and nonsmokers with CD from France and the Netherlands, matched for country, gender, age, disease activity, and body mass index. Fecal DNA was sequenced on an Illumina HiSeq 2500. On average, 40 million paired-end reads were generated per sample. Gene richness and the Shannon index were computed to assess microbial diversity. Wilcoxon's signed-rank tests for paired samples were performed to detect differences between the 2 groups. Results: In total, 21 smoking and 21 nonsmoking patients with CD were included. Compared with nonsmoking patients, gut microbial gene richness (P = 0.01), genus diversity (P < 0.01), and species diversity (P = 0.01) were decreased in smoking patients. This was accompanied by a reduced relative abundance of the genera Collinsella (P = 0.02), Enterorhabdus (P = 0.02), and Gordonibacter (P = 0.02) in smokers. No statistically significant differences at the species level were observed, although smokers had lower proportions of Faecalibacterium prausnitzii (P = 0.10). Conclusions: Gut microbial diversity is reduced in smokers with CD compared with nonsmokers with CD. The microbial profile differs between these groups at the genus level. Future studies should evaluate whether intestinal microbes mediate the adverse effects of smoking in CD. PMID:27542127
Wall, Geoffrey C; Leman, Bernard I
We report a case of sinus mucormycosis in a patient receiving infliximab for Crohn's disease (CD). A 41-year-old white female with a history of gastroesophageal reflux disease, well-controlled diabetes, and ileocecal CD developed right-sided facial pain and high fevers, with computed tomography scan confirming sinusitis. She had been receiving both low-dose azathioprine and scheduled infliximab for her CD. A sinus biopsy was procured endoscopically which grew mucormycosis. All immunosuppressive agents were immediately discontinued, and the patient underwent multiple debridement procedures of the right sinuses. Amphotericin B lipid complex and posaconazole were administered to the patient. Repeat laboratory and imaging study demonstrated clearance of the infection approximately 30 days after diagnosis. The patient's CD did not flair during withdrawal of immunosuppressive medications, and the patient completed 6 months of posaconazole therapy. Clinicians should be aware of the possible development of this potentially catastrophic infection in patients receiving infliximab, especially if such patients have other risks for mucormycosis, such as diabetes. Copyright 2009 S. Karger AG, Basel.
Brecher, Matthew B.; Li, Zhong; Wei, Bo; Nandi, Bisweswar; Zhang, Jing; Ling, Hua; Winslow, Gary; Braun, Jonathan; Li, Hongmin
T cell responses to enteric bacteria are important in inflammatory bowel disease. I2, encoded by the pfiT gene of Pseudomonas fluorescens, is a T-cell superantigen associated with human Crohn's disease. Here we report the crystal structure of pfiT at 1.7Å resolution and provide a functional analysis of the interaction of pfiT and its homolog, PA2885, with human class II MHC. Both pfiT and PA2885 bound to mammalian cells and stimulated the proliferation of human lymphocytes. This binding was greatly inhibited by anti-class II MHC HLA-DR antibodies, and to a lesser extent, by anti HLA-DQ and DP antibodies, indicating that the binding was class II MHC-specific. GST-pfiT efficiently precipitated both endogenous and in vitro purified recombinant HLA-DR1 molecules, indicating that pfiT directly interacted with HLA-DR1. Competition studies revealed that pfiT and the superantigen Mycoplasma arthritidis mitogen (MAM) competed for binding to HLA-DR, indicating that their binding sites overlap. Structural analyses established that pfiT belongs to the TetR-family of DNA-binding transcription regulators. The distinct structure of pfiT indicates that it represents a new family of T cell superantigens. PMID:24385909
Cappello, Maria; Morreale, Gaetano Cristian
In the past, laboratory tests were considered of limited value in Crohn's disease (CD). In the era of biologics, laboratory tests have become essential to evaluate the inflammatory burden of the disease (C-reactive protein, fecal calprotectin) since symptoms-based scores are subjective, to predict the response to pharmacological options and the risk of relapse, to discriminate CD from ulcerative colitis, to select candidates to anti-tumor necrosis factors [screening tests looking for hepatitis B virus and hepatitis C virus status and latent tuberculosis], to assess the risk of adverse events (testing for thiopurine metabolites and thiopurine-methyltransferase activity), and to personalize and optimize therapy (therapeutic drug monitoring). Pharmacogenetics, though presently confined to the assessment of thiopurineme methyltransferase polymorphisms and hematological toxicity associated with thiopurine treatment, is a promising field that will contribute to a better understanding of the molecular mechanisms of the variability in response to the drugs used in CD with the attempt to expand personalized care and precision medicine strategies.
Ma, Jia Yi; Tong, Jin Lu; Ran, Zhi Hua
Along with epidemiological changes in tuberculosis (TB) and an increased incidence of Crohn's disease (CD), the differential diagnosis of intestinal TB (ITB) and CD is of vital importance and has become a clinical challenge because treatment based on misdiagnosis may lead to fatal outcomes. In this study, we reviewed the similarities and differences in clinical, endoscopic, radiological and histological features of these two diseases. Concomitant pulmonary TB, ascites, night sweats, involvement of fewer than four segments of the bowel, patulous ileocecal valve, transverse ulcers, scars or pseudopolyps strongly indicate ITB. Bloody stools, perianal signs, chronic diarrhea, extraintestinal manifestations, anorectal lesions, longitudinal ulcers and a cobblestone appearance are all suggestive of CD. Significant differences in the size, number, location and patterns of granulomas in ITB and CD with regard to their histopathologic features have been noted. Immune stain of cell surface markers is also helpful. Interferon-γ release assay and polymerase chain reaction analysis have achieved satisfactory sensitivity and specificity in the diagnosis of ITB. Computed tomography enterographic findings of segmental small bowel or left colon involvement, mural stratification, the comb sign and fibrofatty proliferation are significantly more common in CD, whereas mesenteric lymph node changes (calcification or central necrosis) and focal ileocecal lesions are more frequently seen in ITB. A diagnosis should be carefully established before the initiation of the therapy. In suspicious cases, short-term empirical anti-TB therapy is quite efficient to further confirm the diagnosis.
Youk, Ada O.; Gonzalez-Heydrich, Joseph; Bujoreanu, Simona I.; Weisz, John; Fairclough, Diane; Ducharme, Peter; Jones, Neil; Lotrich, Francis; Keljo, David; Srinath, Arvind; Bousvaros, Athos; Kupfer, David; DeMaso, David R.
Background: Crohn's disease (CD) is associated with depression. It is unclear if psychosocial interventions offer benefit for depressive symptoms during active CD. In this secondary analysis of a larger study of treating depression in pediatric inflammatory bowel disease, we assessed whether cognitive behavioral therapy (CBT) would differentiate from supportive nondirective therapy in treating depression and disease activity in youth with CD. We also explored whether somatic depressive symptoms showed a different pattern of response in the overall sample and the subset with active inflammatory bowel disease. Methods: Youth with depression and CD (n = 161) were randomized to 3 months of CBT (teaching coping skills) or supportive nondirective therapy (supportive listening). Depressive severity was measured using the Children's Depression Rating Scale-Revised (CDRS-R) with the somatic depressive subtype consisting of those CDRS-R items, which significantly correlated with CD activity. Disease activity was measured by the Pediatric Crohn's disease Activity Index. Given the potential confound of higher dose steroids, subanalyses excluded subjects on >20 mg/d prednisone equivalent (n = 34). Results: Total CDRS-R scores in the overall sample significantly decreased over time after both treatments (P < 0.0001). Treatment with CBT was associated with a significantly greater improvement in the Pediatric Crohn's disease Activity Index (P = 0.05) and somatic depressive subtype (P = 0.03) in those with active inflammatory bowel disease (n = 95) compared with supportive nondirective therapy. After excluding those on steroids (n = 34), there was a significant improvement in total CDRS-R (P = 0.03) and in Pediatric Crohn's disease Activity Index (P = 0.03) after CBT. Conclusions: Psychotherapy may be a useful adjunct to treat depression in the context of CD-related inflammation in youth who are not concurrently on higher dose steroids. PMID:25822010
Lakatos, Peter Laszlo
Over the last some years the increasing knowledge on the pathogenesis of Crohn's disease led to the development of a number of biological agents targeting specific molecules involved in gut inflammation, first of all TNF-alpha and its receptors. Infliximab, adalimumab and certolizumab have been successful in inducing and maintaining remission in Crohn's disease at both short and long term. This was recently confirmed by a Cochrane meta-analysis and also open label extension follow-up and cohort studies. Emerging new data however indicate that combination therapy with infliximab-azathioprine appears to have added benefit in inducing steroid-free remission and mucosal healing than either infliximab or azathioprine alone in azathioprine-naïve patients with early disease. Similarly the combination of steroids induction and infliximab was efficacious in luminal Crohn's disease. In contrast, there seems to be no synergism between methotrexate and infliximab. It is also less clear whether it is beneficial to use short or long-term infliximab-azathioprine combination in patients who previously failed therapy with azathioprine. In contrast, combination may potentially be associated with increased risk for infection and cancer. In case control-studies, especially the combination of steroids and anti-TNF and older age increased the risk for infectious complications, while scattered case reports point to the potentially increased risk of a rare form of non-Hodgkin's lymphoma (Hepatosplenic T cell lymphoma) with the use of azathioprine-anti-TNF combination. The aim of this review is to summarize the benefits and risks for the use combination therapy with TNF-alpha inhibitors in the treatment of Crohn's disease.
Lerner, A; Rossi, T M; Park, B; Albini, B; Lebenthal, E
Serum antibodies to five cow's milk proteins, alpha-casein, bovine serum albumin (BSA), beta-lactoglobulin A and B (BLG-a, BLG-b) and alpha-lactalbumin (ALA) were investigated in young patients with inflammatory bowel disease, 56 with Crohn's disease (CD), 24 with ulcerative colitis (UC). IgG antibodies against BSA and BLG-a and -b were higher in Crohn's disease patients as compared to those with ulcerative colitis and controls. The IgG anti-BSA were higher in the group of CD patients with higher score of disease activity. Additionally, IgA antibodies to alpha-casein were higher in CD and UC compared to control. These findings may be due to increased uptake of dietary antigens or enhanced immunological response occurring in CD patients.
Turck, D.; Ythier, H.; Maquet, E.; Deveaux, M.; Marchandise, X.; Farriaux, J.P.; Fontaine, G.
(/sup 51/Cr)EDTA was used as a probe molecule to assess intestinal permeability in 7 healthy control adults, 11 control children, 17 children with Crohn's disease, and 6 children with untreated celiac disease. After subjects fasted overnight, 75 kBq/kg (= 2 microCi/kg) /sup 51/Cr-labeled EDTA was given by mouth; 24-h urinary excretion of (/sup 51/Cr)EDTA was measured and expressed as a percentage of the total oral dose. Mean and SD were as follows: control adults 1.47 +/- 0.62, control children 1.59 +/- 0.55, and patients with Crohn's disease or celiac disease 5.35 +/- 1.94. The difference between control children and patients was statistically significant (p less than 0.001). These results show that intestinal permeability to (/sup 51/Cr)EDTA is increased among children with active or inactive Crohn's disease affecting small bowel only or small bowel and colon, and with untreated celiac disease. The (/sup 51/Cr)EDTA permeability test could facilitate the decision to perform more extensive investigations in children suspected of small bowel disease who have atypical or poor clinical and biological symptomatology.
Calvet, Xavier; Motos, Jaime; Montserrat, Antònia; Gallardo, Olga; Vergara, Mercedes
Chronic disability and its consequences for social life and employment are important but often neglected aspects of Crohn's disease. No specific scores have been developed to evaluate chronic disability in patients with Crohn's disease; the medical criteria used by government authorities to award disability benefits have not been analyzed. We aimed to determine the courts' criteria for awarding disability benefits to patients with Crohn's disease in Spain. We systematically searched case law databases in Spain's regional Supreme Courts to identify sentences regarding awards of disability benefits to patients with Crohn's disease. Selected decisions were reviewed to extract variables related to the awarding of benefits. Univariate and multivariate analyses were performed to determine which variables predicted the awarding of benefits. Two hundred eighty sentences were reviewed. The rate of judicial decisions in favor of the claimants varied considerably between the various tribunals. Multivariate analysis showed that adequate description of the disease (odds ratio, 8.6), fecal incontinence (odds ratio, 8.9), the number of associated diseases (odds ratio, 2.3), and the presence of an ostomy (odds ratio, not estimable) were independent predictors of the awarding of Social Security benefits. The amount of Social Security benefits awarded to patients with Crohn's disease varied depending on the tribunal. The most important predictors of a court's disability award were the adequate description of the patient's disease, fecal incontinence, associated diseases, and presence of an ostomy.
Tang, Rui-han; Chao, Kang; Zhang, Sheng-hong; Chen, Bai-li; He, Yao; Gao, Xiang; Zeng, Zhi-rong; Hu, Pin-jin; Chen, Min-hu
To investigate the prevalence and characteristics of anemia among patients with Crohn's disease (CD) in Chinese population and identify the possible risk factors. A cross-sectional study was performed in 441 patients with CD enrolled from the First Affiliated Hospital of Sun Yat-Sen University between January 2003 and May 2012. The prevalence, severity, type of anemia in these patients was assessed when diagnosis was confirmed. A multivariate logistic regression including 122 patients was performed to screen risk factors of anemia. The prevalence of anemia was 64.4% (284/441) with 69.0% (196/284) mild anemia, 28.9% (82/284) moderate anemia and 2.1% (6/284) severe anemia. The most common morphological classification was hypochromic microcytic anemia (43.7%, 124/284). Multivariate logistic regression showed the predictive factors for anemia were higher levels of modified Crohn's disease activity index (CDAI) (OR = 1.007, 95% CI 1.002-1.013), platelet count (OR = 1.007, 95% CI 1.001-1.012), erythrocyte sedimentation rate (OR = 1.024, 95% CI 1.000-1.048), penetrating behavior (OR = 16.952, 95% CI 2.626-108.626), structuring behavior (OR = 6.717, 95% CI 1.583-28.507), older age at diagnosis (OR = 1.065, 95% CI 1.012-1.121),and lower body mass index (BMI) (OR = 0.769, 95% CI 0.633-0.935). Anemia is a common complication in patients with CD among Chinese population. Activity of the underlying disease, older age at diagnosis, penetrating or structuring disease behavior and low BMI are the risk factors.
The etiology and pathogenesis of idiopathic chronic-inflammatory bowel diseases, i.e. Crohn's disease and ulcerative colitis, are still unknown. This has no effect on diagnosis, yet does affect treatment of these diseases, which has thus remained symptomatic. Clinical features, laboratory findings, endoscopy in conjunction with histologic examination and radiologic studies are all of proven value in the diagnosis of these disorders. Microbiologic and, if indicated, serologic studies are employed to search for colitis caused by microorganisms. Other bowel disorders to be considered in differential diagnosis include ischemic, radiation and drug-induced forms of colitis, as well as diverticulitis. More recently introduced techniques for the detection of secondary intra-abdominal processes are CT-scan and MRI (magnetic resonance imaging). Ultrasound examination of the abdomen can be used to search for thickening of the bowel wall. Use of the rather complicated hydrocolon sonography is rarely necessary. Endo-sonography is an established method for exploration of the rectum and is particularly useful for the detection of abscesses. The role of this technique in the diagnosis of colon processes remains to be determined. Studies using radiolabeled leukocytes are of theoretical interest but not usually required in the routine work-up of such patients. The same is true of chemical analyses of the feces and testing for antineutrophil cytoplasmic antibodies. Standard systemic treatment is based on the administration of salicylic acid derivatives and corticosteroids. Azathioprine and 6-mercaptopurine can be used in patients refractory to standard treatment. Metronidazole has been proven quite effective in patients with Crohn's disease of the colon, particularly in the perianal region.(ABSTRACT TRUNCATED AT 250 WORDS)
Zhu, Chenjing; Ma, Xuelei; Xue, Luqi; Xu, Jing; Li, Qingfang; Wang, Yun; Zhang, Jing
Crohn disease (CD) is a chronic relapsing disease. Imaging modalities are essential for the diagnosis and assessment of CD. Small intestine contrast ultrasonography (SICUS) is a well-tolerated, noninvasive and radiation-free modality and has shown potential in CD assessment. We aimed at evaluating the diagnostic accuracy of SICUS in the detection and assessment of small-bowel lesions and complications in CD. We searched PubMed database for relevant studies published before April 24, 2016. We integrated the true positive, false positive, false negative, and true negative into the pooled estimates of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio. Forest plots were to represent the pooled results of all studies. Thirteen articles were finally considered eligible. The pooled sensitivity and specificity of SICUS in detecting small-bowel lesions were 0.883 (95% confidence interval (CI) 0.847-0.913) and 0.861 (95% CI 0.828-0.890), respectively. The pooled diagnostic odds ratio was 39.123 (95% CI 20.014-76.476) and the area under the curve of summary receiver operating characteristic was 0.9273 (standard error: 0.0152). In subgroup analyses, SICUS represented fine sensitivity and specificity in proximal and distal small intestine lesion, as well as in CD-related complications such as stricture, dilation, abscess, and fistula. SICUS is accurate enough to make a complete assessment about the location, extent, number, and almost all kinds of complications in CD small-bowel lesions.
Lionetti, Paolo; Callegari, Maria Luisa; Ferrari, Susanna; Cavicchi, Maria Chiara; Pozzi, Elena; de Martino, Maurizio; Morelli, Lorenzo
Exclusive enteral nutrition (EN) is an established primary therapy for pediatric Crohn's disease (CD). The mechanism of action of such treatment is still conjectural. The aim of the present study was to investigate if EN-induced remission is associated with modification of the fecal microflora in CD. Stool samples were collected from 5 healthy children and adolescents over a period of 3 months, and from 9 children and adolescents with active CD. To induce disease remission, children with CD received a course of exclusive EN for 8 weeks with a polymeric formula (Modulen IBD, Nestlè). At the end of the course of exclusive EN, children returned to a free diet but continued to take 40% of the daily caloric intake as polymeric formula. Fecal microflora was analyzed by 16S ribosomal DNA polymerase chain reaction and temperature gradient gel electrophoresis (TGGE) with direct visual comparison of band profiles of PCR products. In 8 of 9 children, the exclusive EN alone induced disease remission. In 1 child, it was necessary to add steroids to the exclusive EN course to achieve remission. In all children with CD, analysis of gel band distribution revealed profound modification of the fecal microflora after exclusive EN. Variations of band distribution corresponding to different bacterial species were observed also in children on partial EN and required time to achieve stability of the band profile. In contrast, control healthy children showed a host-specific and stable TGGE profile over time. These data suggest that a possible mechanism of action of EN in inducing disease remission in CD is the capacity of modification of gut microflora. Possible explanations of such capacity are both low residue and prebiotic properties of the polymeric liquid formula.
Dubinsky, Marla C; Lin, Ying-Chao; Dutridge, Debra; Picornell, Yoana; Landers, Carol J; Farrior, Sharmayne; Wrobel, Iwona; Quiros, Antonio; Vasiliauskas, Eric A; Grill, Bruce; Israel, David; Bahar, Ron; Christie, Dennis; Wahbeh, Ghassan; Silber, Gary; Dallazadeh, Saied; Shah, Praful; Thomas, Danny; Kelts, Drew; Hershberg, Robert M; Elson, Charles O; Targan, Stephan R; Taylor, Kent D; Rotter, Jerome I; Yang, Huiying
Crohn's disease (CD) is a heterogeneous disorder characterized by diverse clinical phenotypes. Childhood-onset CD has been described as a more aggressive phenotype. Genetic and immune factors may influence disease phenotype and clinical course. We examined the association of immune responses to microbial antigens with disease behavior and prospectively determined the influence of immune reactivity on disease progression in pediatric CD patients. Sera were collected from 196 pediatric CD cases and tested for immune responses: anti-I2, anti-outer membrane protein C (anti-OmpC), anti-CBir1 flagellin (anti-CBir1), and anti-Saccharomyces-cerevisiae (ASCA) using ELISA. Associations between immune responses and clinical phenotype were evaluated. Fifty-eight patients (28%) developed internal penetrating and/or stricturing (IP/S) disease after a median follow-up of 18 months. Both anti-OmpC (p < 0.0006) and anti-I2 (p < 0.003) were associated with IP/S disease. The frequency of IP/S disease increased with increasing number of immune responses (p trend = 0.002). The odds of developing IP/S disease were highest in patients positive for all four immune responses (OR (95% CI): 11 (1.5-80.4); p = 0.03). Pediatric CD patients positive for > or =1 immune response progressed to IP/S disease sooner after diagnosis as compared to those negative for all immune responses (p < 0.03). The presence and magnitude of immune responses to microbial antigens are significantly associated with more aggressive disease phenotypes among children with CD. This is the first study to prospectively demonstrate that the time to develop a disease complication in children is significantly faster in the presence of immune reactivity, thereby predicting disease progression to more aggressive disease phenotypes among pediatric CD patients.
Ram, Roopa; Sarver, David; Pandey, Tarun; Guidry, Carey L; Jambhekar, Kedar R
Crohn's disease (CD) is a chronic inflammatory bowel disease that often requires frequent imaging of patients in order to detect active disease and other complications related to disease activity. While endoscopy is the gold standard for diagnosis, it may be contraindicated in some patients and has a limited role in detecting deep submucosal/mesenteric diseases and intra abdominal complications. In recent years, magnetic resonance enterography (MRE) has evolved as a noninvasive, radiation free imaging modality in the evaluation of patients with CD. This review article will focus on role of MRE in imaging patients with CD with emphasis on technical considerations, systematic image interpretation, differential diagnoses, and the role of imaging in deciding treatment options for patients. PMID:27413262
Wensinck, F.; Van de Merwe, J. P.
Sera from patients suffering from Crohn's and other diseases and from healthy subjects were tested for agglutinins to anaerobic, gram-positive coccoid rods belonging to species of Eubacterium and Peptostreptococcus. Four strains labelled Eubacterium contortum (two strains), Eubacterium rectale and Peptostreptococcus productus were agglutinated by a higher percentage of sera from patients with Crohn's disease than from healthy subjects and from patients with liver and intestinal diseases (including ulcerative colitis), ankylosing spondylitis, granulomatous diseases, diseases of immunity and malignancies. The agglutinins were of the IgG and IgM classes and strain-specific; the titres were low. The results obtained with sera from patients with Crohn's disease and healthy people were subjected to discriminant analysis to estimate the probability, based on the combined results with the four strains, that a patient suffers from Crohn's disease. When sera giving an a posteriori probability greater than or equal to 0.95 (a priori probability = 0.5) were considered positive, the test with four strains had a sensitivity of 54% and a specificity of nearly 100%. The results with sera submitted for diagnosis showed that positive reactions in patients with a diagnosis apparently incompatible with Crohn's disease were within acceptable limits. PMID:7019318
Müller, Katalin Eszter; Lakatos, Péter László; Papp, Mária; Veres, Gábor
Epitheloid granulomas are one of the best histological criteria for distinguishing Crohn's disease from other inflammatory bowel diseases. However, the role of granuloma in the pathogenesis and clinical characteristics of Crohn's disease is unclear. The aim of the present study was to evaluate the frequency of granulomas and their association with clinical characteristics using the database of the Hungarian Pediatric Inflammatory Bowel Disease Registry. Three hundred and sixty-eight children with Crohn's disease were registered between January 1st, 2007 and December 31st, 2010. The frequency of granulomas was 31.4% (111/353) at diagnosis. Isolated granuloma in the upper gastrointestinal tract was detected in 2.5% of patients, while those in the terminal ileum was found in 5% of patients. There was no difference in location, behavior and disease activity indexes between patients with and without granulomas. Need for immunomodulators and biological therapy was similar in the two groups in the first year of diagnosis. The frequency of granulomas in this cohort was comparable to the frequency reported in other studies. Interestingly, granulomas in the terminal ileum or upper gastrointestinal tract contributed to the diagnosis of Crohn's disease in one of 13 children. These data indicate that multiple biopsies from multiple sites are essential for the diagnosis of pediatric Crohn's disease.
Seemann, Natashia M; King, Sebastian K; Elkadri, Abdul; Walters, Thomas; Fish, Joel; Langer, Jacob C
Perianal Crohn's disease (PCD) can affect both quality of life and psychological wellbeing. A subset of pediatric patients with complex PCD require surgical intervention, although appropriate timing and treatment regimens remain unclear. This study aimed to describe a large pediatric cohort in a tertiary center to determine the range of surgical management in children with complex PCD. A retrospective review of children requiring operative intervention for PCD over 13 years (2002-2014) was performed. PCD was divided into simple and complex based on the type of surgical procedure, and the two groups were compared. The 57 children were divided into two groups: the simple group (N=43) underwent abscess drainage ± seton insertion alone, and the complex group (N=14) underwent loop ileostomy ± more extensive surgery. In the complex group, females were more predominant (57% of complex vs 30% of simple), and the average age at diagnosis was lower. Anti-TNF therapy was utilized in 79.1% of simple and 100% of complex PCD. All 14 complex patients underwent a defunctioning ileostomy, with 7 requiring further operations (subtotal colectomy=4, proctocolectomy ± anal sparing=5, plastic surgery reconstruction with perineal flap/graft=4). Complex PCD represents a small but challenging subset of patients in which major surgical intervention may be necessary to alleviate the symptoms of this debilitating condition. retrospective case study with no control group - level IV. Copyright Â© 2016 Elsevier Inc. All rights reserved.
Eder, Piotr; Banasiewicz, Tomasz; Matysiak, Konrad; Łykowska-Szuber, Liliana
Anal fistulas occurring in Crohn's disease (CD) comprise a risk factor of severe course of inflammation. They are frequently intractable due to various factors such as penetration of the anal canal or rectal wall, impaired wound healing, and immunosuppression, among others. Anal fistulas typical to CD develop from fissures or ulcers of the anal canal or rectum. Accurate identification of the type of fistula, such as low and simple or high and complex, is crucial for prognosis as well as for the choice of treatment. If fistulotomy remains the gold standard in the surgical treatment of the former, it is contraindicated in high and complex fistulas due to possible risk of damage to the anal sphincter with subsequent faecal incontinence. Therefore, the latter require a conservative and palliative approach, such as an incision and drainage of abscesses accompanying fistulas or prolonged non-cutting seton placement. Currently, conservative, sphincter-preserving, and definitive procedures such as mucosal advancement or dermal island flaps, the use of plugs or glue, video assisted anal fistula treatment, ligation of the intersphincteric track, and vacuum assisted closure are gaining a great deal of interest. Attempting to close the internal opening without injuring the sphincter is a major advantage of those methods. However, both the palliative and the definitive procedures require adjuvant therapy with medical measures. PMID:26557938
Aljebreen, Abdulrahman M; Alharbi, Othman R; Azzam, Nahla A; Almalki, Ahmed S; Alswat, Khalid A; Almadi, Majid A
Despite the remarkable increase in the incidence of Crohn's disease among Saudis in recent years, data about Crohn's disease in Saudi Arabia are scarce. The aim of this study was to determine the clinical epidemiology and phenotypic characteristics of Crohn's disease in the central region of Saudi Arabia. A data registry, Inflammatory Bowel Disease Information System (IBDIS), was used to register Crohn's disease patients who presented to the gastroenterology clinics in four tertiary care centers in Riyadh, Saudi Arabia between September 2009 and February 2013. Patients' characteristics, disease location, behavior, age at diagnosis according to the Montreal classification, course of the disease, and extraintestinal manifestation were recorded. Among 497 patients with Crohn's disease, 59% were males with a mean age at diagnosis of 25 years [95% Confidence Interval (CI): 24-26, range 5-75 years]. The mean duration from the time of complaint to the day of the diagnosis was 11 months, and the mean duration of the disease from diagnosis to the day of entry to the registry was 40 months. Seventy-seven percent of our patients were aged 17-40 years at diagnosis, 16.8% were ≤16 years of age, and 6.6% were >40 years of age. According to the Montreal classification of disease location, 48.8% of patients had ileocolonic involvement, 43.5% had limited disease to the terminal ileum or cecum, 7.7% had isolated colonic involvement, and 16% had an upper gastrointestinal involvement. Forty-two percent of our patients had a non-stricturing, non-penetrating behavior, while 32.8% had stricturing disease and 25.4% had penetrating disease. Crohn's disease is frequently encountered in Saudi Arabia. The majority of patients are young people with a predilection for males, while its behavior resembled that of western societies in terms of age of onset, location, and behavior.
Schoon, E; Muller, M; Vermeer, C; Schurgers, L; Brummer, R; Stockbrugger, R
BACKGROUND—A high prevalence of osteoporosis is reported in Crohn's disease. The pathogenesis is not completely understood but is probably multifactorial. Longstanding Crohn's disease is associated with a deficiency of fat soluble vitamins, among them vitamin K. Vitamin K is a cofactor in the carboxylation of osteocalcin, a protein essential for calcium binding to bone. A high level of circulating uncarboxylated osteocalcin is a sensitive marker of vitamin K deficiency. AIMS—To determine serum and bone vitamin K status in patients with Crohn's disease and to elucidate its relationship with bone mineral density. METHODS—Bone mineral density was measured in 32 patients with longstanding Crohn's disease and small bowel involvement, currently in remission, and receiving less than 5 mg of prednisolone daily. Serum levels of vitamins D and K, triglycerides, and total immunoreactive osteocalcin, as well as uncarboxylated osteocalcin ("free" osteocalcin) were determined. The hydroxyapatite binding capacity of osteocalcin was calculated. Data were compared with an age and sex matched control population. RESULTS—Serum vitamin K levels of CD patients were significantly decreased compared with normal controls (p<0.01). "Free" osteocalcin was higher and hydroxyapatite binding capacity of circulating osteocalcin was lower than in matched controls (p<0.05 and p<0.001, respectively), indicating a low bone vitamin K status in Crohn's disease. In patients, an inverse correlation was found between "free" osteocalcin and lumbar spine bone mineral density (r=−0.375, p<0.05) and between "free" osteocalcin and the z score of the lumbar spine (r=−0.381, p<0.05). Multiple linear regression analysis showed that "free" osteocalcin was an independent risk factor for low bone mineral density of the lumbar spine whereas serum vitamin D was not. CONCLUSIONS—The finding that a poor vitamin K status is associated with low bone mineral density in longstanding Crohn
Vaiopoulou, Anna; Gazouli, Maria; Papadopoulou, Aggeliki; Anagnostopoulos, Athanassios K; Karamanolis, George; Theodoropoulos, George E; M'Koma, Amosy; Tsangaris, George T
Crohn disease (CD) and ulcerative colitis (UC), known collectively as inflammatory bowel diseases (IBDs), are chronic immunoinflammatory pathologies of unknown aetiology. Despite the frequent use of biomarkers in medical practice, there is a relative lack of information regarding validated paediatric biomarkers for IBD. Furthermore, biomarkers proved to be efficacious in adults are frequently extrapolated to the paediatric clinical setting without considering that the pathogenesis of many diseases is distinctly different in children. In the present study, proteomics technology was used to monitor differences in protein expression among adult and young patients with CD, identify a panel of candidate protein biomarkers that may be used to improve prognostic-diagnostic accuracy, and advance paediatric medical care. Male and female serum samples from 12 adults and 12 children with active CD were subjected to 2-dimensional gel electrophoresis. Following the relative quantitation of protein spots exhibiting a differential expression between the 2 groups by densitometry, the spots were further characterized by matrix-assisted laser desorption tandem time-of-flight mass spectrometer. The results were confirmed by Western blot analysis. Clusterin was found to be significantly overexpressed in adults with CD, whereas ceruloplasmin and apolipoprotein B-100 were found to be significantly overexpressed in children, indicating that the expression of these proteins may be implicated in the onset or progression of CD in these 2 subgroups of patients. Interestingly, we found a differential expression of several proteins in adults versus paediatric patients with CD. Undoubtedly, future experiments using a larger cohort of patients with CD are needed to evaluate the relevance of our preliminary findings.
Lee, Young Ah; Chun, Peter; Hwang, Eun Ha; Mun, Sang Wook; Lee, Yeoun Joo
Purpose The aim of this study was to investigate the clinical features and extraintestinal manifestations (EIMs) of Crohn disease (CD) in Korean pediatric patients. Methods The medical records of 73 children diagnosed with CD were retrospectively reviewed. Data regarding baseline demographic and clinical characteristics, including CD phenotype at diagnosis based on the Montreal classification, and clinical features and course of EIMs were investigated. Results Fifty-two (71.2%) of the patients were males. The mean age of the patients was 12.5 years. The mean follow-up period was 3.4 years. The disease location was ileal in 3 (4.1%) of the patients, colonic in 13 (17.8%), ileocolonic in 56 (76.7%). The clinical behavior was inflammatory in 62 (84.9%) of the patients, stricturing in 8 (11.0%), and penetrating in 3 (4.1%). Perianal abscesses or fistulas were found in 37 (50.7%) of the patients. EIMs observed during the study period were anal skin tag in 25 patients (34.2%), hypertransaminasemia in 20 (27.4%), peripheral arthritis in 2 (2.7%), erythema nodosum in 2 (2.7%), vulvitis in 1 (1.4%), uveitis in 1 (1.4%), and pulmonary thromboembolism in 1 (1.4%). Conclusion Perianal diseases and manifestations were present in more than half of Korean pediatric CD patients at diagnosis. Inspection of the anus should be mandatory in Korean children with suspicious CD, as perianal fistulas, abscesses, and anal skin tags may be the first clue to the diagnosis of CD. PMID:28090468
Casellas, F; Guarner, F; Antolín, M; Rodríguez, R; Salas, A; Malagelada, J R
The mucosal release of inflammatory mediators is enhanced in active inflammatory bowel disease. This study examines whether leukotriene C4 production occurs in apparently unaffected segments of the gut. The intraluminal release of leukotriene C4 was determined by jejunal perfusion in seven healthy controls, in nine patients with chronic ulcerative colitis, and in 13 patients with Crohn's disease (six with ileal disease, and seven with only colonic). All patients were in clinical remission and none of them had evidence of jejunal involvement. Mild intraluminal irritation with a 2.5 mmol/l deoxycholic acid solution was induced to stimulate local inflammatory mechanisms. The release of DNA (a marker of mucosal desquamation) and prostaglandin E2 (PGE2) was simultaneously measured. Jejunal release of DNA was higher in Crohn's disease patients than in ulcerative colitis or healthy controls. Basal release of PGE2 was similar in the three groups of patients. Basal release of leukotriene C4 was considerably enhanced, however, in Crohn's disease patients compared with healthy controls. In ulcerative colitis patients, basal leukotriene C4 release was non-significantly different from controls. Bile acid perfusion stimulated PGE2, leukotriene C4, and DNA release in all groups studied, but leukotriene C4 release was significantly higher in Crohn's disease patients. It is concluded that in inactive Crohn's disease there is an enhanced intraluminal release of leukotriene C4 in apparently unaffected segments of proximal small bowel, which may reflect fundamental changes in the function of the gut mucosal barrier. PMID:8174991
Esteban, J M; Maldonado, L; Sanchiz, V; Minguez, M; Benages, A
The aim of this study was to evaluate with colour Doppler ultrasound the vascular changes in the wall of the loops affected by Crohn's disease, and to establish whether these changes reflects clinical or biochemical activity of Crohn's disease. Seventy-nine patients with Crohn's disease (44 with active disease and 35 inactive patients) were studied with frequency- and amplitude-encoded duplex Doppler sonography. A group of 35 healthy volunteers were also included. The exam consisted of the search for colour signals in the walls of the loops affected by Crohn's disease, classifying the degree of vascularity with a simple scoring system into three groups: absence of colour signal (score of 0); weak or scattered colour signals (score of 1); and multiple colour signals or clear identification of vessels in the loops walls (score of 2). Doppler curves were obtained of the detected vessels with measurement of the resistive index (RI). There was a visible increase in the gut walls' vascularity in the active patients compared with those with inactive disease. The mean RI was statistically significantly lower in the gut wall vessels of the patients with active illness than that obtained in the inactive patients. Colour Doppler ultrasound is a useful tool in the assessment of activity in Crohn's disease.
Lazebnik, L B; Boldyreva, O N; Parfenov, A I; Trubitsyna, I E; Shcherbakov, P L; Khomeriki, S G; Kniazev, O V; Sagynbaeva, V É
The treatment of inflammatory bowel diseases (IBD), which include ulcerative colitis (UC) and Crohn's disease (CD) is one of actual problems of modern gastroenterology and coloproctology. In recent years a great attention is paid to the molecules of adhesion. Adhesion proteins play a significant role in the development of inflammation in patients with IBD. They cause the migration of cells from the capillaries into the center of inflammation, i.e. do much to increase the inflammatory infiltration of the mucosa and homing of lymphocytes. Changes in the levels of adhesion factors under the influence of biological therapy have been insufficiently studied. So the aim of our study was to determine the diagnostic value of adhesion molecules--integrin-sVCAM-1 and selectins P-, E-, L- for the assessment of the effectiveness of therapy in patients with UC and CD and prognosis of the disease. 15 patients with IBD were examined (15 patients with Crohn's disease (CD)). 9 patients were treated using infliximab 5 mg/kg according to the standard scheme (0-2-6 and then every 8 weeks). 3 patients with IBD received anti-inflammatory therapy with the introduction of the culture of MSC in the number of 150 x 108 cells suspended in 200 ml of physiological solution with the addition of heparin (10 IU/ml). 3 patients received azathioprine (2 mg/kg) and glucocorticosteroids (GCS) 1 mg/kg. The clinical symptoms, the level of leukocytes, erythrocyte sedimentation rate, C-reactive protein and also were analyzed before and after the treatment with infliximab and transplantation of MSC. The status of the colonic mucosa was evaluated using colonoscopy with biopsy. The concentration of adhesion molecules L-selectin, E-selectin, P-selectin, integrin-sVCAM-1 in blood serum was analyzed using immunoenzyme method twice before the beginning of treatment and after 2 months. It is established that after the standard therapy with the use of corticosteroids and azathioprine clinical and laboratory signs
Ahmed, Osman; Rodrigues, David Mario
Introduction. Crohn's disease is most commonly found in the terminal ileum and colonic region. Magnetic resonance has become a useful modality for assessing small bowel activity. In this study, we performed a systematic review and meta-analysis on the use of MR in detecting small bowel activity as well as extramural complications in Crohn's patients. Methods. Two independent reviewers sorted through articles until October 2, 2014. We included both studies providing raw data for pooling and studies without raw data. Sensitivity, specificity, likelihood ratios, and 95% confidence intervals were calculated for each study. Results. There were 27 included studies, of which 19 were included in the pooled analysis. Pooled analysis of the 19 studies (1020 patients) with raw data revealed a sensitivity of 0.88 (95% CI 0.86 to 0.91) and specificity was 0.88 (95% CI 0.84 to 0.91). In regard to detecting stenosis, pooled sensitivity was 0.65 (95% CI 0.53 to 0.76) and specificity was 0.93 (95% CI 0.89 to 0.96). Conclusion. MR imaging provides a reliable alternative in detecting small bowel activity in patients with Crohn's disease. Its advantages include high diagnostic accuracy and no radiation exposure while its disadvantages include high cost and limited availability. PMID:27446869
Dieckgraefe, Brian K; Korzenik, Joshua R; Husain, Asif; Dieruf, Lisa
Glycogen storage disease (GSD)-1b has been associated with neutropenia and abnormalities of neutrophil function. Many individuals with GSD-1b manifest chronic gastrointestinal inflammation. Our study was performed to precisely establish the type, frequency, and spectrum of gastrointestinal disease in patients with GSD-lb. We established a medical database of 36 individuals affected with GSD-1b, utilizing patients at our center, disease registries, and direct contacts with North American referral centers specializing in genetic disorders. Records were reviewed, focusing on documentation of gastrointestinal involvement. Gastrointestinal symptoms or manifestations were present in approximately 75% of the patients, including chronic abdominal pain and diarrhea, perianal fistula or abscess, and oral aphthous ulceration. Of patients identified, 28% had documented inflammatory bowel disease (IBD) and an additional 22% of patients had symptoms highly suggestive of IBD, but had not undergone comprehensive diagnostic evaluation. Gastrointestinal involvement was found to be indistinguishable from idiopathic Crohn disease (CD) by detailed review of clinical, radiologic, endoscopic and histopathologic findings. Many patients had significant improvement or resolution of gastrointestinal disease in response to G-CSF treatment. The expression of CD in patients with GSD-1b may be delayed or prevented by G-CSF treatment. a strong association exists between glycogen storage disease type 1b and inflammatory bowel disease. A high index of suspicion for Crohn disease should be applied in evaluating patients with glycogen storage disease type 1b and intestinal symptoms. These results provide further support for the hypothesis that some forms of inflammatory bowel disease may result from impaired mucosal innate immunity. Additional investigations into the intestinal disease in glycogen storage disease type 1b may be directly relevant to the etiology and treatment of idiopathic Crohn
Parés, David; Shamali, Awad; Flashman, Karen; O'Leary, Daniel; Senapati, Asha; Conti, John; Parvaiz, Amjad; Khan, Jim
The aim of our study was to analyse the short-term outcomes of laparoscopic surgery for a no medical responding ileocolic Cohn's disease in a single centre according to the presence of obesity. A cross-sectional study was performed including all consecutive patients who underwent laparoscopic resection for ileocecal Crohn's disease from November 2006 to November 2015. Patients were divided according to body mass index ≥ 30 kg/m(2) in order to study influence of obesity in the short-term outcomes. The following variables were studied: characteristics of patients, surgical technique and postoperative results (complications, reintervention, readmission and mortality) during first 30 postoperative days. A total of 100 patients were included (42 males) with a mean age of 39.7±15.2 years (range 18-83). The overall complication rate was 20% and only 3 patients had an anastomotic leak. Seven patients needed reoperation in the first 30 days postop (7%). The median postoperative length of hospitalization was 5.0 days. Operative time was significantly longer in patients with obesity (130 vs. 165minutes, P=.007) but there were no significant differences among the postoperative results in patients with and without obesity. This study confirmed that laparoscopic approach for ileocecal Cohn's disease is a safety and feasible technique in patients with obesity. In this last group of patients we only have to expect a longer operative time. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.
Hugot, J.P.; Laurent-Puig, P.; Gower-Rousseau, C.; Caillat-Zueman, S.; Beaugerie, L.; Dupas, J.L.; Van Gossum, A.; Bonaiti-Pellie, C.; Cortot, A.
Segregation analyses of familial aggregations of Crohn disease have provided consistent results pointing to the involvement of a predisposing gene with a recessive mode of inheritance. Although extensively investigated, the role played by human leucocyte antigen (HLA) genes in this inflammatory bowel disease remains elusive and the major histocompatibility complex is a candidate region for the mapping of the Crohn disease susceptibility gene. A total of 25 families with multiple cases of Crohn disease was genotyped for HLA DRB1 and for 16 highly polymorphic loci evenly distributed on chromosome 6. The data were subjected to linkage analysis using the lod score method. Neither individual nor combined lod scores for any family and for any locus tested reached values suggesting linkage or genetic heterogeneity. The Crohn disease predisposing locus was excluded from the whole chromosome 6 with lod scores less than -2. It was excluded from the major histocompatibility complex and from 91% of the chromosome 6 genetic map with lod scores less than -4. The major recessive gene involved in genetic predisposition to Crohn disease does not reside on the major histocompatibility complex nor on any locus mapping to chromosome 6. 37 refs., 2 figs., 2 tabs.
Levine, Arie; Broide, Efrat; Stein, Michal; Bujanover, Yoram; Weizman, Zvi; Dinari, Gabriel; Pacht, Avi; Branski, David; Zahavi, Ilan
Oral budesonide has been found to be efficacious for mild to moderate Crohn's disease in adults, with equal improvement rates for budesonide and prednisone. We report the results of a retrospective study of budesonide treatment in mild to moderate Crohn's disease in children. Charts of patients treated with budesonide (n = 62) with a pediatric Crohn's Disease Activity Index of 12.5 to 40 were compared with a cohort of 58 age-matched patients treated with prednisone. Among children treated with budesonide, 48% had remission compared with 77% of the children treated with prednisone (P =.001). Among patients who had failed previous medical therapy with mesalamine, 59% had remission with budesonide (9 mg/day). Remission with prednisone occurred in 73% of children who failed to achieve remission with budesonide. Patients responding to budesonide had significantly milder disease compared with nonresponders who had remission while taking prednisone. Budesonide is useful in mild to moderate Crohn's disease in children. It is more effective than mesalamine and antibiotics but less effective than prednisone. Budesonide should be considered for first-line therapy in mild to moderate Crohn's disease.
Tan, C X W; Brand, H S; de Boer, N K H; Forouzanfar, T
Widely varying prevalence rates of oral lesions in patients with Crohn's disease have been reported, ranging from 0.5% to 37%. These manifestations may coincide with or precede intestinal symptoms. Oral manifestations can be classified as specific lesions, when macroscopic examination shows similar changes to those observed endoscopically in the intestine, and non-specific lesions including aphthous ulcerations. The most frequently observed oral lesions are oedema, ulcers and hyperplastic lesions on the buccal mucosa. In most patients these lesions are asymptomatic, however, some patients may experience discomfort. In this review we describe the most relevant oro-dental manifestations observed in patients with Crohn's disease and discuss the potential implications for oro-dental management.
Sechi, Leonardo A.; Manuela, Mura; Francesco, Tanda; Amelia, Lissia; Antonello, Solinas; Giovanni, Fadda; Stefania, Zanetti
Crohn's disease is a chronic inflammatory disease of the gastrointestinal tract of unknown etiology. We report on the presence of cell wall-deficient Mycobacterium avium subsp. paratuberculosis in 35 of 48 paraffin-embedded tissue specimens from 33 patients with Crohn's disease by in situ hybridization with IS900 as a probe. PMID:11724871
Crama-Bohbouth, G; Bosman, F T; Vermeer, B J; van der Wal, A M; Biemond, I; Weterman, I T; Peńa, A S
Biopsies of apparently normal buccal mucosa were taken from 14 patients with Crohn's disease and 13 healthy controls who were matched for dental status. Most patients had an increased number of lymphocytes around vessels in the subepithelial tissue and two showed fibrosis with moderate atrophy of minor glands. Plasma cells which contained immunoglobulin, predominantly IgA, were only found around minor salivary glands in both patients and controls. Quantitative studies showed a significant increase in the number of cells containing IgA in patients compared with controls. No correlation was found between immunoglobulin pattern and disease activity, age, sex, or duration of Crohn's disease. A significant correlation was found between the activity of the disease, as defined by the Crohn's Disease Activity Index, and the number of plasma cells containing IgM.
Wang, Feng; Kaplan, Jess L; Gold, Benjamin D; Bhasin, Manoj K; Ward, Naomi L; Kellermayer, Richard; Kirschner, Barbara S; Heyman, Melvin B; Dowd, Scot E; Cox, Stephen B; Dogan, Haluk; Steven, Blaire; Ferry, George D; Cohen, Stanley A; Baldassano, Robert N; Moran, Christopher J; Garnett, Elizabeth A; Drake, Lauren; Otu, Hasan H; Mirny, Leonid A; Libermann, Towia A; Winter, Harland S; Korolev, Kirill S
The relationship between the host and its microbiota is challenging to understand because both microbial communities and their environments are highly variable. We have developed a set of techniques based on population dynamics and information theory to address this challenge. These methods identify additional bacterial taxa associated with pediatric Crohn disease and can detect significant changes in microbial communities with fewer samples than previous statistical approaches required. We have also substantially improved the accuracy of the diagnosis based on the microbiota from stool samples, and we found that the ecological niche of a microbe predicts its role in Crohn disease. Bacteria typically residing in the lumen of healthy individuals decrease in disease, whereas bacteria typically residing on the mucosa of healthy individuals increase in disease. Our results also show that the associations with Crohn disease are evolutionarily conserved and provide a mutual information-based method to depict dysbiosis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Lewis, James D; Chen, Eric Z; Baldassano, Robert N; Otley, Anthony R; Griffiths, Anne M; Lee, Dale; Bittinger, Kyle; Bailey, Aubrey; Friedman, Elliot S; Hoffmann, Christian; Albenberg, Lindsey; Sinha, Rohini; Compher, Charlene; Gilroy, Erin; Nessel, Lisa; Grant, Amy; Chehoud, Christel; Li, Hongzhe; Wu, Gary D; Bushman, Frederic D
Abnormal composition of intestinal bacteria--"dysbiosis"-is characteristic of Crohn's disease. Disease treatments include dietary changes and immunosuppressive anti-TNFα antibodies as well as ancillary antibiotic therapy, but their effects on microbiota composition are undetermined. Using shotgun metagenomic sequencing, we analyzed fecal samples from a prospective cohort of pediatric Crohn's disease patients starting therapy with enteral nutrition or anti-TNFα antibodies and reveal the full complement and dynamics of bacteria, fungi, archaea, and viruses during treatment. Bacterial community membership was associated independently with intestinal inflammation, antibiotic use, and therapy. Antibiotic exposure was associated with increased dysbiosis, whereas dysbiosis decreased with reduced intestinal inflammation. Fungal proportions increased with disease and antibiotic use. Dietary therapy had independent and rapid effects on microbiota composition distinct from other stressor-induced changes and effectively reduced inflammation. These findings reveal that dysbiosis results from independent effects of inflammation, diet, and antibiotics and shed light on Crohn disease treatments.
Crama-Bohbouth, G; Bosman, F T; Vermeer, B J; van der Wal, A M; Biemond, I; Weterman, I T; Peńa, A S
Biopsies of apparently normal buccal mucosa were taken from 14 patients with Crohn's disease and 13 healthy controls who were matched for dental status. Most patients had an increased number of lymphocytes around vessels in the subepithelial tissue and two showed fibrosis with moderate atrophy of minor glands. Plasma cells which contained immunoglobulin, predominantly IgA, were only found around minor salivary glands in both patients and controls. Quantitative studies showed a significant increase in the number of cells containing IgA in patients compared with controls. No correlation was found between immunoglobulin pattern and disease activity, age, sex, or duration of Crohn's disease. A significant correlation was found between the activity of the disease, as defined by the Crohn's Disease Activity Index, and the number of plasma cells containing IgM. PMID:6826103
Brown, Ian S; Miller, Gregory C; Bettington, Mark L; Rosty, Christophe
Crohn's disease is a chronic inflammatory disorder that can affect any part of the gastrointestinal tract. Our objective was to review the histological findings in index biopsies from the terminal ileum and other gastro-intestinal tract sites of Crohn's disease patients prior any treatment and to compare them with the findings from patients with non-specific ileitis. A total of 111 consecutive Crohn's disease cases (55 females, median age 27 years) with extra-ileal biopsies were retrospectively selected. Upper gastrointestinal inflammatory changes were found in 68 % of gastric biopsies, 60 % of oesophageal biopsies and 43 % of duodenal biopsies with no significant difference in frequency between paediatric and adult cases. Crohn's colitis was more common in paediatric cases than adult cases (85 % versus 57 %). Granuloma in at least one extra-ileal site was observed in 40 %, more frequently in paediatric cases than in adults (78 vs 27 %). Compared with Crohn's disease cases, the group of 151 non-specific ileitis cases (75 females, median age 52 years) were more likely to have normal upper and lower gastrointestinal biopsies and to show less frequent crypt architectural changes in the terminal ileum. In summary, Crohn's disease ileitis is often associated with inflammation elsewhere in the gastrointestinal tract while non-specific ileitis was infrequently associated with inflammation elsewhere for both paediatric and adult patients. These findings support the role of systematic biopsies in multiple gastrointestinal sites to help distinguishing Crohn's ileitis from non-specific ileitis in paediatric and adult population.
Ozturk, Ersin; Cakir, Ozcan; Mutlu, Hakan; Sonmez, Guner; Sildiroglu, H Onur; Basekim, C Cinar; Kizilkaya, Esref
The goal of our study was to compare the accuracy of computed tomography enteroclysis (CTE) to that of biopsy in detecting bowel wall alterations of the terminal ileum in Crohn's disease (CD). A total of 43 patients with either diagnosed or suspected CD (16 females, 28 males) underwent CTE and ileoscopy. Ileoscopy diagnosed 35 patients with CD of the ileum, while 8 patients served as the control group. Computed tomography enteroclysis detected CD in 31 patients (88%) and in none of the control group. According to the criteria used for evaluation of small bowel loop distension, 31 cases were (72%) with optimal distension, nine cases (%21) with good distension, and three cases (7%) with poor distension. Computed tomography enteroclysis showed that mean ileal wall thickness in patients with CD was 6.8 mm (range, 9.5-4.1 mm) and 1.79 mm in patients in the control group (range, 2.20-1.38 mm). Mean postcontrast wall density in patients with CD was 81.9 HU (range, 111.6-52.2 HU) and 41.1 HU (range, 49.8-22.4 HU) in the control group. Mean postcontrast wall density in 17 patients with active CD was 97 HU (range, 67-123 HU) and 62 HU (range, 46-87 HU) in 18 CD patients in remission. We calculated that the overall sensitivity and specificity of CTE in detecting the severity of CD were 89% and 100%, respectively. Positive predictive value was 100%; negative predictive value was 89%. Our results indicate that CTE can reveal CD involvement of small bowel accurately and allow assessment of the degree of disease activity.
Dorofeyev, A. E.; Vasilenko, I. V.; Rassokhina, O. A.; Kondratiuk, R. B.
Background. The mucus layer in the gastrointestinal tract plays important role in host innate defense, regulation of secretion, and absorption processes, maintaining colonization resistance, which composes the integrity of protective mucus barrier in the large intestine. Investigations of mucin expression in the colon mucosa can improve the understanding of protective function of mucosal barrier in ulcerative colitis (UC) and Crohn's disease (CD). Materials and Methods. 77 patients with UC and CD were examined. Histological analysis of colon mucosa was done by standard method (haematoxylin-eosin, alcian blue at pH 1.0 and 2.5 to determine sulfated and nonsulfated glycosaminoglycans and glycoproteins, and goblet cells). To characterize the mucus production the PAS-reaction was performed. Immunohistochemistry was performed using monoclonal mouse antibodies raised against MUC2, MUC3, MUC4, and TFF3 (USBiological, USA). Results. The moderate expression of MUC2 and MUC3 (50.0% and 32.1%, P = 0.03) and high expression of MUC4 and TFF3 in the colon mucosa were observed in all patients with CD. The intensive labeling of MUC4 and TFF3 occurred more often (42.9% and 57.1%, P = 0.03) in patients with CD. The level of expression of secretory MUC2 and transmembrane MUC3 and MUC4 in all patients with UC was low, up to its complete absence (59.2% and 53.1% cases, P = 0.05). TFF3 expression had high and medium staining intensity in patients with UC. Conclusions. Different types of mucins synthesis, secretion, and expression were found in patients with UC and CD. The expression of mucin MUC2, MUC3, MUC4, and TFF3 correlated with the activity of disease and the extent of the inflammatory process in the large intestine. The most pronounced alteration of mucins expression was observed in patients with severe UC and CD. PMID:23737764
Bromberg, S H; Faroud, S; de Castro, F F; Morrone, N; de Godoy, A C; França, L C
Isolated ileocecal involvement by tuberculosis in the absence of pulmonar disease is rare in Brasil, therefore causes a diagnostic dilemma as it mimics colonic malignancy and Crohn's disease. Between 1969 and 1989, eight patients with isolated hypertrophic ileocecal tuberculosis were treated by surgery in the Gastroenterology Surgery Department of the HSPE-FMO. The most common complaint among them was abdominal pain (100%) with associated symptoms of weight loss (62.5%); nausea, vomiting, fever and general weekness appeared in half of the patients. A right iliac fossa mass was present in seven (87.5% ) of them. The mean duration of symptoms was 14.7 month (range 5-36 months). In all eight patients chest x-rays were negative for tuberculosis. Barium contrast studies showed abnormalities in all cases, but these could not be distinguished from carcinoma. Colonoscopy was helpful in establishing the diagnosis of suboclusive lesions of the ileocecal regions in three patients. Tuberculosis diagnosis was suspected in two of them because ofr the presence of granulomas in colonic biopsy material. Six patients were submitted to elective right hemicolectomy. The two remaining with suspect of tuberculosis were operated with signals of intestinal occlusion, and underwent a limited ileocaecal resection. The positive diagnosis of intestinal tuberculosis was made in all the patients by identification of acid-fast bacilli and by the presence of caseating granulomas in intestinal or lymph node tissue on histological examination. The outcome in all of them was favorable. They received treatment with three antituberculosis drugs over a twelve month period. Hypertrophic ileocecal tuberculosis must still be considered in the differential diagnosis of abdominal pathology localized in the right lower quadrant.
Short, Scott S; Dubinsky, Marla C; Rabizadeh, Shervin; Farrior, Sharmayne; Berel, Dror; Frykman, Philip K
Perianal perforating disease (PF) has been reported in approximately 15% of children with Crohn's disease (CD). It is unknown whether children who present with PF at the time of diagnosis have a different course than those that develop PF while on therapy. From a prospective, single institution observational registry of children diagnosed with CD, we identified children with perianal perforating CD, defined as perianal abscesses and/or fistulae. Patients who presented with perianal perforating CD (PF-CD0) were compared to those who developed perianal perforating CD (PF-CD1) after initial diagnosis. Thirty-eight of 215 (18%) children with CD had PF-CD during a median follow up of 4.5 years. Patients with PF-CD0 (n=26) tended to be more likely male (81% vs. 50%, p=0.07) and younger (9.3 yrs vs. 12.5 yrs, p=0.02). PF-CD1 (n=12) patients were more likely to require diverting ileostomy (42% vs. 8%, p=0.02) and colectomy (33% vs. 4%, p=0.03). Multivariable analysis predicted increased rate of diverting ileostomy in the PF-CD1 group (p=0.007, OR 19.1, 95% CI 1.6-234.8). Pediatric CD patients who develop PF while on therapy for CD have a more severe phenotype and are more likely to require diverting ileostomy or colectomy compared to those who present with PF-CD. Copyright © 2013 Elsevier Inc. All rights reserved.
Allen, Brian C; Leyendecker, John R
Magnetic resonance enterography (MRE) utilization has increased for the evaluation of small bowel diseases over the last several years. In addition to performing similarly to computed tomography enterography (CTE) in the evaluation of inflammatory bowel disease, MRE lacks ionizing radiation, can image the small bowel dynamically, and provides excellent soft tissue contrast resolution. This article reviews imaging protocols for MRE, normal MR imaging appearance of small bowel, and the imaging findings of small bowel Crohn disease. The importance of imaging findings for directing management in patients with small bowel Crohn disease is emphasized throughout.
Hammer, Matthew R; Dillman, Jonathan R; Smith, Ethan A; Al-Hawary, Mahmoud M
Noninvasive, nonionizing, multiparametric magnetic resonance (MR) imaging of the pelvis using a field strength of 3 T now provides a comprehensive assessment of perineal involvement in pediatric Crohn disease. MR imaging accurately evaluates inflammatory disease activity, and allows determination of the number and course of fistula tracts as well as their relationships to vital perianal structures, including the external anal sphincter, helping to guide surgical management and improve outcomes. This article provides an up-to-date review of perineal MR imaging findings of Crohn disease in the pediatric population, including fistulous disease, abscesses, and skin manifestations. Imaging technique is also discussed.
Patil, Seema A; Cross, Raymond K
The development of penetrating Crohn's disease (CD) occurs in up to 50% of patients over the course of their lifetime. While the presentation of these complications, including free perforation, intra-abdominal abscess, and enteric fistula, are usually obvious, the management can require a nuanced approach, with distinct short and long-term approaches. Areas covered: This review discusses medical and surgical methods of treating these complications, including the role of percutaneous drainage of abscesses, the implications of a stricture associated with a fistula, and the efficacy of postoperative anti-TNF therapy in preventing recurrence after surgical treatment. Expert commentary: An approach to the management of these complications that begins with control of sepsis, including broad-spectrum antibiotics, bowel rest, and nutritional support is proposed. The next appropriate step is a diagnostic evaluation to determine the utility of medical versus surgical therapy, considering the presence of a stricture and prior immunosuppressive therapy. Postoperative anti-TNF therapy, a highly effective method to prevent recurrence, should be considered in many cases.
Gabrecht, Tanja; Borle, Francois; van den Bergh, Hubert; Michetti, Pierre; Ortner, Maria-Anna; Wagnières, Georges
Crohn's disease is an inflammatory bowel disease originating from an overwhelming response of the mucosal immune system. Low dose photodynamic therapy (PDT) may modify the mucosal immune response and thus serve as a therapy for Crohn's disease. Most patients with Crohn's disease show inflammatory reactions in the terminal ileum or colon where PDT treatment is feasible by low-invasive endoscopic techniques. However, the tube like geometry of the colon, it's folding, and the presences of multiple foci of Crohn's lesions along the colon require the development of adequate light delivery techniques. We present a prototype light delivery system for endoscopic clinical PDT in patients with Crohn's disease. The system is based on a cylindrical light diffuser inserted into a diffusing balloon catheter. Homogenous irradiation is performed with a 4 W diode laser at 635 nm. Light dosimetry is performed using a calibrated integrating sphere. The system can be used with conventional colonoscopes and colonovideoscopes having a 3.8 mm diameter working channel. The feasibility of PDT in colon with our prototype was demonstrated in first clinical trials.
Bühner, S; Nagel, E; Körber, J; Vogelsang, H; Linn, T; Pichlmayr, R
In patients with active Crohn's disease and in a control group the fatty acid profiles in the whole lipid fraction of ileal and colonic mucosal biopsy specimens were determined by capillary gas chromatography. The biopsy specimens in Crohn's disease patients were taken from the inflamed terminal ileum as well as from the inflamed and macroscopically normal colon. Compared with controls the fatty acid distribution in the inflamed ileal mucosa was significantly characterised by (a) a decrease of 18:2 n6 and 18:3 n3 accompanied by a substantial increase of the highly polyunsaturated fatty acids 20:4 n6, 22:4 n6, and 22:6 n3 and (b) a higher unsaturation index of total fatty acids compared with controls. These changes were similar in the inflamed colon. Additionally, both the inflamed and the macroscopically normal colonic mucosa showed an increase of saturated (18:0) and a decrease of monounsaturated fatty acids (18:1 n9). Fatty acid profiles of ileum and colon showed side variations in controls, but not in the Crohn's disease group. These data suggest that in Crohn's disease changes in the distribution of polyunsaturated fatty acids seem to be the general feature of inflamed mucosa in small and large intestine. Results further suggest that colonic fatty acid metabolism in Crohn's disease is altered by degrees, showing changes in saturated and monounsaturated fatty acids as an additional, primary event. PMID:7959199
Dettmer, M; Hegemann, I; Hegemann, S C A
Patients with autoimmune inner ear disease develop rapidly progressive sensorineural hearing loss over a period of several weeks or months, often accompanied by vestibular loss. This disease can occur as a distinct clinical entity or in association with an underlying autoimmune disorder. Treatment comprises immunosuppression by corticosteroids, cytostatic drugs or tumor necrosis factor-α antagonists. We report histopathological and immunohistochemical findings of the inner ear of a patient with a granulomatous inner ear disease suffering from Crohn's disease that was nonresponsive to treatment and who underwent surgery for bilateral cochlear implants.
Ławnicka, Izabela; Książek, Andrzej
Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis of unknown aetiology, often related to the antineutrophil cytoplasmic antibody (ANCA). GPA was previously named Wegener's granulomatosis (WG). The disease frequently has multisystemic presentation, targeting mainly the respiratory tract and kidneys, but gastrointestinal involvement is uncommon. Crohn's disease (CD) is an inflammatory bowel disease (IBD) with many extraintestinal manifestations. Clinically, symptoms of WG and CD can mimic each other. In this paper a case of GPA manifested initially by severe multiorgan damage including colitis, regarded to be coexistent CD, is presented. The case illustrates the difficulties in establishing the diagnosis when symptoms of the diseases mimic each other. PMID:27407286
Jóźwiak, Lucyna; Ławnicka, Izabela; Książek, Andrzej
Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis of unknown aetiology, often related to the antineutrophil cytoplasmic antibody (ANCA). GPA was previously named Wegener's granulomatosis (WG). The disease frequently has multisystemic presentation, targeting mainly the respiratory tract and kidneys, but gastrointestinal involvement is uncommon. Crohn's disease (CD) is an inflammatory bowel disease (IBD) with many extraintestinal manifestations. Clinically, symptoms of WG and CD can mimic each other. In this paper a case of GPA manifested initially by severe multiorgan damage including colitis, regarded to be coexistent CD, is presented. The case illustrates the difficulties in establishing the diagnosis when symptoms of the diseases mimic each other.
Körner, Meike; Rehmann, Ruth; Reubi, Jean Claude
Peptide hormones of the glucagon-like peptide (GLP) family play an increasing clinical role, as reported for GLP-1 in diabetes therapy and insulinoma diagnostics. GLP-2, despite its known trophic and anti-inflammatory intestinal actions translated into preliminary clinical studies using the GLP-2 analogue teduglutide for treatment of short bowel syndrome and Crohn's disease, remains poorly characterized in terms of expression of its receptor in tissues of interest. Therefore, the GLP-2 receptor expression was assessed in 237 tumor and 148 non-neoplastic tissue samples with in vitro receptor autoradiography. A GLP-2 receptor expression was present in 68% of gastrointestinal stromal tumors (GIST). Furthermore, GLP-2 receptors were identified in the intestinal myenteric plexus, with significant up-regulation in active Crohn's disease. The GLP-2 receptors in GIST may be used for clinical applications like in vivo targeting with radiolabelled GLP-2 analogues for imaging and therapy. Moreover, the over-expressed GLP-2 receptor in the myenteric plexus may represent the morphological correlate of the clinical target of teduglutide in Crohn's disease.
Villanueva-Lozano, Hiram; Treviño-Rangel, Rogelio de J; Hernández-Balboa, Cristina L; González, Gloria M; Martínez-Reséndez, Michel F
We present a case report of a fungal bloodstream infection due to an unusual pathogen. This is a 30 years-old female patient diagnosed with Crohn's disease and a disseminated Mycobacterium bovis infection subsequently complicated by fungemia due to the emergent yeast pathogen Candida ciferrii, who was unresponsive to fluconazole and made a full recovery after treatment with posaconazole. To our knowledge, this is the first report of Candida ciferrii isolation from blood in an adult associated to a central venous catheter and which was successfully treated with posaconazole.
Russo, Irene; Ferrazzi, Anna; Zanetti, Irene; Alaibac, Mauro
Epidermolysis bullosa acquisita is a rare, acquired, autoimmune subepidermal blistering disease of the skin, characterised by blisters and erosions, especially in trauma-prone sites and extensor skin surface, scarring with formation of milia, skin fragility and nail dystrophy. Epidermolysis bullosa acquisita is extremely rare in childhood and it has been reported to be frequently associated with Crohn's disease. Furthermore, autoantibodies against type VII collagen have been found in a large number of patients with Crohn's disease without epidermolysis bullosa acquisita. We report a case of a 17-year-old boy affected by Crohn's disease who presented with milia on infiltrated erythematous plaques over the back of the hands. The diagnosis of epidermolysis bullosa acquisita was confirmed by histopathology, direct and indirect immunofluorescence analysis and ELISA. 2015 BMJ Publishing Group Ltd.
Rindos, Noah; Ecker, Amanda; Carter, Gloria; Mansuria, Suketu
We present an interesting case of a 35-year-old nulligravida with Crohn's disease with ovarian involvement. This is a rare manifestation of Crohn's disease, felt to arise from fistulization between the ovary and the intestine, most commonly the ileum. Our review of the literature revealed 11 additional case reports published in English with a total of 15 cases. The mean age at time of presentation was 33.7 years, with a predominance of right-sided involvement. This series included 10 patients with affected right ovaries, 3 with affected left ovaries, and 2 with bilateral involvement. We conclude that ovarian involvement in Crohn's disease, although rare, can exist, and that the gynecologic surgeon should be aware of this relevant disease manifestation.
Um, Yoo Jin; Kim, Sun Moon; Pyo, Jin Sil; Lee, Joo Ah; Koo, Hoon Sup; Huh, Kyu Chan
Peutz-Jeghers syndrome is an autosomal dominant inherited disorder characterized by multiple gastrointestinal hamartomatous polyps and mucocutaneous pigmentation. Peutz-Jeghers syndrome has an incidence of approximately 1 in 25,000 to 300,000 births. Crohn's disease is a chronic inflammatory bowel disease that typically manifests as regional enteritis with its incidence ranging from 3.1 to 14.6 cases per 100,000 person-years in North America. Herein, we report a case of a 30-year-old male patient who had both Peutz-Jeghers syndrome and Crohn's disease. We believe that this is the first case in Korea and the second report in the English literatures on Peutz-Jeghers syndrome coincidentally accompanied by Crohn's disease.
Patterson, Emily R; Shmidt, Eugenia; Oxentenko, Amy S; Enders, Felicity T; Smyrk, Thomas C
To assess a possible association between inflammatory bowel disease (IBD) and the histologic finding in duodenal biopsy specimens of increased intraepithelial lymphocytes (IELs) with normal villous architecture. We identified all patients with duodenal biopsy specimens obtained between 2000 and 2010 showing increased IELs and normal architecture. Among the 74 such patients who also had IBD, we characterized the clinical features of IBD and reviewed all available upper gastrointestinal biopsy specimens. Fifty-eight patients had Crohn disease, 13 had ulcerative colitis, and three had IBD, type unclassified. No duodenal sample with increased IELs had other histologic features of IBD. Among gastric biopsy specimens from 34 patients with Crohn disease, nearly half (16) had focal gastritis. We propose that Crohn disease be included in the differential diagnosis for increased IELs with normal villous architecture in duodenal biopsy specimens, particularly when gastric biopsy specimens show focal gastritis. Copyright© by the American Society for Clinical Pathology.
Cioffi, Ugo; De Simone, Matilde; Ferrero, Stefano; Ciulla, Michele M; Lemos, Alessandro; Avesani, Ettore Contessini
Background Several malignancies have been described in association with inflammatory bowel diseases, the most common being adenocarcinoma. Carcinoid tumor and Crohn disease has also been previously reported, however the coexistence of both neoplasms is quite rare and the clinical diagnosis is very difficult. Here we report what we believe to be the fourth case of a mixed adenocarcinoid tumor coexisting with Crohn's disease. Case report The patient presented with clinical and radiological features of intestinal obstruction. Laparotomy showed a stricturing lesion in the last 6 cm of the terminal ileum with proximal dilation. Only the histology of the resected surgical specimen proved the presence of a mixed adenocarcinoid tumor involving the terminal ileum. Conclusion Carcinoid tumor should be suspected in elderly patients with Crohn's disease presenting with intestinal obstruction and laparotomy should be considered to exclude malignancy. PMID:16336666
Bianco, Anna Monica; Zanin, Valentina; Girardelli, Martina; Magnolato, Andrea; Martelossi, Stefano; Martellossi, Stefano; Tommasini, Alberto; Marcuzzi, Annalisa; Crovella, Sergio
Crohn's disease (CD) is a multifactorial disease, in which environmental, microbial and genetic factors play important roles. CD is characterized by a chronic granulomatous inflammation by necrotic scarring with aspects of full-thickness wall. In spite of affecting mainly young adults, sometimes, CD can be present in the first year of life (early onset Crohn disease, EOCD) showing an unpredictable course and being often more severe than at older ages. In this paper we propose the hypothesis that EOCD patients should be analyzed using a Mendelian approach with family studies aimed to identify new loci directly involved in the early onset Crohn's disease. So we will leave the classic association study approach used until now for the identification of genes responsible for susceptibility to CD and propose linkage family analysis as alternative and powerful tool for the identification of new genetic variants associated with familiar cases of EOCD.
Lazzerini, Marzia; Bramuzzo, Matteo; Ventura, Alessandro
To review pediatric cases of orofacial granulomatosis (OFG), report disease characteristics, and explore the association between OFG and Crohn's disease. We conducted a systematic review according to the PRISMA guidelines. We searched Medline, LILACS, Virtual Health Library, and Web of Knowledge in September 2013 for cases of OFG in the pediatric age range (< 18 years), with no language limitations. All relevant articles were accessed in full text. The manual search included references of retrieved articles. We extracted data on patients' characteristics, disease characteristics, association with other diseases, and treatment. We analyzed the data and reported the results in tables and text. We retrieved 173 reports of OFG in children. Mean age at onset was 11.1 ± 3.8 years (range: 2.0-18 years). Prevalence in males was significant higher than in females (P < 0.001), with a male:female ratio of 2:1. Gastrointestinal signs or symptoms were present in 26.0% of children at the time of OFG diagnosis. Overall, 70/173 (40.4%) children received a concomitant diagnosis of Crohn's disease. In about half (51.4%) of the cases the onset of OFG anticipated the diagnosis of Crohn's disease, with a mean time between the two diagnoses of 13.1 ± 11.6 mo (range: 3-36 mo). Overall, 21/173 (12.1%) of the children with OFG had perianal disease, while 11/173 (6.4%) had a family history of Crohn's disease. Both perianal disease and a family history of Crohn's disease were significantly associated with a higher risk of Crohn's disease diagnosis in children with OFG [relative risk (RR) = 3.10, 95% confidence interval (CI): 2.46-3.90; RR = 2.74, 95%CI: 2.24-3.36, P < 0.0001 for both). Treatment of OFG included steroids (70.8% of children) and other immunosuppressive drugs (42.7%), such as azathioprine, thalidomide and infliximab. High prevalence of Crohn's disease in children with OFG suggests that OFG may be a subtype of Crohn's disease.
Molendijk, Ilse; Nuij, Veerle J A A; van der Meulen-de Jong, Andrea E; van der Woude, C Janneke
Despite potent drugs and surgical techniques, the treatment of perianal fistulizing Crohn's disease (CD) remains challenging. We assessed treatment strategies for perianal fistulizing CD and their effect on remission, response, and relapse. Patients with perianal fistulizing CD visiting the Erasmus MC between January 1, 1980 and January 1, 2000 were identified. Demographics, fistula characteristics, and received treatments aimed at the outcome of these strategies were noted. In total, 232 patients were identified (98 male; 42.2%). Median follow-up was 10.0 years (range, 0.5-37.5 yr). Complex fistulas were present in 78.0%. Medical treatment (antibiotics, steroids, immunosuppressants, and anti-tumor necrosis factor) commenced in 79.7% of the patients and in 53.2%, surgery (colectomy, fistulectomy, stoma, and rectum amputation) was performed. Simple fistulas healed more often than complex fistulas (88.2% versus 64.6%; P < 0.001). Rectum involvement was not associated with a lower remission rate, and anti-tumor necrosis factor therapy did not increase complete fistula healing rates in simple and complex fistula. Initially, healed fistulas recurred in 26.7% in case of simple fistulas and in 41.9% in case of complex fistulas (P = 0.051). Only 37.0% of the complex fistulas were in remission at the end of follow-up compared with 66.7% of the simple fistulas (P < 0.001). Only the minority of CD complex perianal fistulas were in remission after conventional treatment strategies after a median follow-up of 10 years. Simple fistulas were more likely to heal than complex fistulas, and less of these healed fistulas relapsed. However, more than 3 quarters of the patients had complex perianal fistulas.
Kristo, Ivan; Riss, Stefan; Argeny, Stanislaus; Maschke, Svenja; Chitsabesan, Praminthra; Stift, Anton
AIM To evaluate frequency and clinical course of incidental adenocarcinoma in patients with stricturing Crohn's disease (CD). METHODS In this study, consecutive patients, who were operated on for stricturing CD between 1997-2012, were included at an academic tertiary referral center. Demographic data and clinical course were obtained by an institutional database and individual chart review. Besides baseline characteristics, intraoperative findings and CD related history were also recorded. Colorectal cancer was classified and staged according to the Union for International Cancer Control (UICC). RESULTS During the study period 484 patients underwent resections due to stricturing CD. Incidental adenocarcinoma was histologically confirmed in 6 (1.2%) patients (4 males, 2 females). Patients diagnosed with colorectal cancer had a median age of 43 (27-66) years and a median history of CD of 16 (7-36) years. Malignant lesions were found in the rectum (n = 4, 66.7%), descending colon (n = 1, 16.7%) and ileocolon (n = 1, 16.7%). According to the UICC classification two patients were stages as I (33.3%), whereas the other patients were classified as stage IIA (16.7%), stage IIIB (16.7%), stage IIIC (16.7%) and stage IV (16.7%), respectively. After a median follow-up of 2 (0.03-8) years only 1 patient is still alive. CONCLUSION The frequency of incidental colorectal cancer in patients, who undergo surgery for stenotic CD, is low but associated with poor prognosis. However, surgeons need to be aware about the possibility of malignancy in stricturing CD, especially if localized in the rectum. PMID:28210083
Juste, Catherine; Kreil, David P; Beauvallet, Christian; Guillot, Alain; Vaca, Sebastian; Carapito, Christine; Mondot, Stanislas; Sykacek, Peter; Sokol, Harry; Blon, Florence; Lepercq, Pascale; Levenez, Florence; Valot, Benoît; Carré, Wilfrid; Loux, Valentin; Pons, Nicolas; David, Olivier; Schaeffer, Brigitte; Lepage, Patricia; Martin, Patrice; Monnet, Véronique; Seksik, Philippe; Beaugerie, Laurent; Ehrlich, S Dusko; Gibrat, Jean-François; Van Dorsselaer, Alain; Doré, Joël
No Crohn's disease (CD) molecular maker has advanced to clinical use, and independent lines of evidence support a central role of the gut microbial community in CD. Here we explore the feasibility of extracting bacterial protein signals relevant to CD, by interrogating myriads of intestinal bacterial proteomes from a small number of patients and healthy controls. We first developed and validated a workflow-including extraction of microbial communities, two-dimensional difference gel electrophoresis (2D-DIGE), and LC-MS/MS-to discover protein signals from CD-associated gut microbial communities. Then we used selected reaction monitoring (SRM) to confirm a set of candidates. In parallel, we used 16S rRNA gene sequencing for an integrated analysis of gut ecosystem structure and functions. Our 2D-DIGE-based discovery approach revealed an imbalance of intestinal bacterial functions in CD. Many proteins, largely derived from Bacteroides species, were over-represented, while under-represented proteins were mostly from Firmicutes and some Prevotella members. Most overabundant proteins could be confirmed using SRM. They correspond to functions allowing opportunistic pathogens to colonise the mucus layers, breach the host barriers and invade the mucosae, which could still be aggravated by decreased host-derived pancreatic zymogen granule membrane protein GP2 in CD patients. Moreover, although the abundance of most protein groups reflected that of related bacterial populations, we found a specific independent regulation of bacteria-derived cell envelope proteins. This study provides the first evidence that quantifiable bacterial protein signals are associated with CD, which can have a profound impact on future molecular diagnosis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Schunk, K; Kern, A; Heussel, C P; Kalden, P; Orth, T; Wanitschke, R; Thelen, M
To compare the value of hydro-MRI with that of barium studies in patients with Crohn's disease. After an oral bowel opacification using 1000 ml of a 2.5% mannitol solution, axial and coronal breath-hold sequences (T2W HASTE +/- FS, contrast-enhanced T1W FLASH FS) were acquired in 46 patients with Crohn's disease at 1.0 T. The findings of hydro-MRI were compared with those of barium studies. In the stomach and the small bowel, hydro-MRI and barium studies demonstrated similar numbers of Crohn's involvements (39 vs. 36); in the colon, hydro-MRI showed clearly more affections (23 vs. 10). Hydro-MRI showed 12.7 cm of inflamed bowel per patient, on average (barium studies: 10.4 cm; p = 0.004). There was a good agreement between the two methods regarding the assessment of the extent of Crohn's disease and the severity of bowel stenoses (r = 0.89 and 0.88, respectively). For the assessment of Crohn's disease, hydro-MRI is preferable to the barium study because of the superior imaging quality and the lack of radiation exposure.
Colussi, Orianne; Rouen, Alexandre; Seksik, Philippe; Cosnes, Jacques; Beaugerie, Laurent; Sokol, Harry
Gastrointestinal symptoms occurring in patients with Crohn's disease (CD) can be related to disease activity or to intercurrent infection. Absence of appropriate stool work-up can lead to misdiagnosis and wrong treatment. We report here two cases of acute cryptosporidiosis in patients with CD. This microorganism can trigger IBD flare or cause severe infections in immunocompromised host. Adding specific search for oocysts of Cryptosporidium parvum using the Ziehl-Neelsen technique to the microbiologic work-up from stools in patients with Crohn's disease seeking medical intervention for sudden exacerbation of digestive symptoms seems to be recommended. Copyright © 2010. Published by Elsevier B.V.
Belai, A; Boulos, P B; Robson, T; Burnstock, G
BACKGROUND: There have been conflicting results regarding the effect of Crohn's disease on the neurochemical composition of the enteric nervous system. AIMS: To examine the effect of Crohn's disease on the neurochemical composition of enteric nerve fibres and cell bodies using whole mount preparations of human ileum. METHODS: Whole wall ileum from seven normal subjects and nine patients with Crohn's disease was used to investigate the neurochemical composition of neurones and nerve fibres in the myenteric plexus, circular muscle, and serosa layer of ileum using immunohistochemical techniques. RESULTS: Increased tyrosine hydroxylase, 5-hydroxytryptamine, and neuropeptide Y immunoreactivity was exclusively seen in the myenteric plexus. There was increased neurofilament immunoreactivity in the myenteric plexus and nerve fibres of the circular muscle layer, and thick bundles of immunoreactive nerve fibres in the serosa layer. Increased vasoactive intestinal polypeptide, nitric oxide synthase, and pituitary adenylate cyclase activating peptide immunoreactivity was seen in the myenteric plexus and nerve fibres of the circular muscle layer, and aggregates of inflammatory cells in the serosa layer of the afflicted segment of Crohn's ileum. In addition, there was a chaotic display of nerve fibres containing some of the neuroactive substances with a high frequency of enlarged varicosities in the myenteric ganglia and/or nerve fibres of the circular muscle layer of Crohn's ileum. CONCLUSION: Results show quantitative as well as qualitative changes in the neurochemical composition of enteric nerve fibres and nerve cell bodies of Crohn's ileum. These changes and the presence of nitric oxide synthase and peptides immunoreactive inflammatory cells in the serosa layer suggest that nerve-immune interactions may have a significant role in the process of the inflammatory changes seen in Crohn's ileitis. Images PMID:9245931
Myrelid, P; Dufmats, M; Lilja, I; Grinn, C; Lannerstad, O; Sjödahl, R
The role of TNF-alpha in Crohn disease is now well established and anti-TNF-alpha is frequently used as a second- or third-line treatment. Tumor necrosis factor-alpha (TNF-alpha) is traditionally associated with macrophages but has recently also been found in mast cells of the ileal wall in patients with Crohn disease. As it is well known that mast cells and TNF-alpha play important roles in atopic manifestations like asthma, allergic rhinitis; and eczema the aim of this study was to investigate whether these are seen more commonly in Crohn patients than in the general population. Patients with Crohn disease (n = 308), aged 18-50 years, living in the Linköping region in southeast Sweden, were asked to answer a questionnaire regarding the presence of any kind of atopic manifestations. The questionnaire was also sent to 930 controls collected from the Southeastern Region Population Registry. The controls were matched according to age, sex, and place of residence. The response rate among the Crohn patients was 91% (280/308) and among controls 84% (779/930). Eczema was a significantly more frequent manifestation, being almost twice as common in Crohn patients (27%) as in the general population (16%). Adjustment by logistic regression for place of residence, gender, age and coexistence of any other atopic manifestation did not change the odds ratios significantly. Atopic manifestations as a group, and eczema as a single manifestation, are significantly more frequent in Crohn patients than in the general population.
Cleynen, Isabelle; Boucher, Gabrielle; Jostins, Luke; Schumm, L Philip; Zeissig, Sebastian; Ahmad, Tariq; Andersen, Vibeke; Andrews, Jane M; Annese, Vito; Brand, Stephan; Brant, Steven R; Cho, Judy H; Daly, Mark J; Dubinsky, Marla; Duerr, Richard H; Ferguson, Lynnette R; Franke, Andre; Gearry, Richard B; Goyette, Philippe; Hakonarson, Hakon; Halfvarson, Jonas; Hov, Johannes R; Huang, Hailang; Kennedy, Nicholas A; Kupcinskas, Limas; Lawrance, Ian C; Lee, James C; Satsangi, Jack; Schreiber, Stephan; Théâtre, Emilie; van der Meulen-de Jong, Andrea E; Weersma, Rinse K; Wilson, David C; Parkes, Miles; Vermeire, Severine; Rioux, John D; Mansfield, John; Silverberg, Mark S; Radford-Smith, Graham; McGovern, Dermot P B; Barrett, Jeffrey C; Lees, Charlie W
Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases. This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34,819 patients (19,713 with Crohn's disease, 14,683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype-phenotype associations across 156,154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile. After quality control, the primary analysis included 29,838 patients (16,902 with Crohn's disease, 12,597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for inflammatory bowel disease showed strong association with
Cleynen, Isabelle; Boucher, Gabrielle; Jostins, Luke; Schumm, L Philip; Zeissig, Sebastian; Ahmad, Tariq; Andersen, Vibeke; Andrews, Jane M; Annese, Vito; Brand, Stephan; Brant, Steven R; Cho, Judy H; Daly, Mark J; Dubinsky, Marla; Duerr, Richard H; Ferguson, Lynnette R; Franke, Andre; Gearry, Richard B; Goyette, Philippe; Hakonarson, Hakon; Halfvarson, Jonas; Hov, Johannes R; Huang, Hailang; Kennedy, Nicholas A; Kupcinskas, Limas; Lawrance, Ian C; Lee, James C; Satsangi, Jack; Schreiber, Stephan; Théâtre, Emilie; van der Meulen-de Jong, Andrea E; Weersma, Rinse K; Wilson, David C; Parkes, Miles; Vermeire, Severine; Rioux, John D; Mansfield, John; Silverberg, Mark S; Radford-Smith, Graham; McGovern, Dermot P B; Barrett, Jeffrey C; Lees, Charlie W
Summary Background Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases. Methods This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34 819 patients (19 713 with Crohn's disease, 14 683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype–phenotype associations across 156 154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile. Findings After quality control, the primary analysis included 29 838 patients (16 902 with Crohn's disease, 12 597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for
Fujimura, Y; Kamoi, R; Iida, M
BACKGROUND--The mechanism of ulceration in Crohn's disease remains unknown. AIMS--To clarify the role of the follicle associated epithelium (FAE) of colonic lymphoid nodules in the formation of ulcers in Crohn's disease. METHODS--After identification of colonic lymphoid nodules and aphthoid lesions by magnifying colonoscopy, 76 biopsy specimens were obtained from 10 patients with Crohn's disease and three patients with colonic lymphoid hyperplasia. This study correlated magnifying colonoscopic, electron microscopic, and immunohistochemical findings of biopsy specimens. RESULTS--In Crohn's disease, scanning electron microscopy of lymphoid nodules surrounded by a red halo without visible erosions by magnifying colonoscopy, showed surface erosions 150-200 microns in size. These lymphoid nodules with red halos had small erosions either light microscopically or electron microscopically in 18 of 21 specimens (86%). Correlation of scanning and transmission electron microscopy showed residues of FAE including M cells at the edges of the erosions. In immunohistochemical studies, HLA-DR antigen was limited in M cells of FAE in the patients with lymphoid hyperplasia without inflammatory bowel disease. In Crohn's disease patients in remission, however, HLA-DR antigen was strongly expressed over the entire FAE of lymphoid nodules with a red halo endoscopically, while the expression was weak and irregular in the mucosa surrounding the lymphoid nodules. HLA-DR was strongly expressed in the entire inflamed colonic mucosa in the active stage. CONCLUSION--The red halo appearance surrounding lymphoid follicles seems to precede visible aphthoid ulcers and suggests that ulcerations in Crohn's disease originate from FAE, possibly related to its physiological role as a portal of entry for potentially pathogenic agents. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:8707119
Benjamin, Jane L; Hedin, Charlotte R H; Koutsoumpas, Andreas; Ng, Siew C; McCarthy, Neil E; Hart, Ailsa L; Kamm, Michael A; Sanderson, Jeremy D; Knight, Stella