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Pregnancy and inflammatory bowel disease.

PURPOSE OF REVIEW: Inflammatory bowel disease commonly affects women during the childbearing years, and young couples are often concerned about the potential effects of inflammatory bowel disease on fertility, pregnancy, and the fetus. This review will critically consider advances over the past 2 years in our knowledge of the effects of inflammatory bowel disease on fertility and pregnancy outcome and the safety and efficacy of medical therapy in the pregnant woman with inflammatory bowel disease. RECENT FINDINGS: The past several years have witnessed significant additions to our knowledge of the effects of ulcerative colitis and Crohn disease on fetal outcome. In addition, important studies have added to the growing database pointing to the overall safety of medical therapy with aminosalicylates and immunomodulators during pregnancy. Limited new data also suggest that inadvertent exposure to infliximab appears not to be harmful to the fetus. SUMMARY: Women with Crohn disease appear to be at risk for early delivery and low birthweight infants, and women with ulcerative colitis may be at increased risk for giving birth to children with congenital abnormalities. The clinical significance of these results may be diluted, however, by inability to adequately assess the confounding influence of disease activity or drug treatment. Despite lingering concerns, the most recent data support the overall safety of the 5-aminosalicylate drugs as well as azothiaprine/6-mercaptopurine during pregnancy. Despite these advances, the potential complications of inflammatory bowel disease and its therapies during pregnancy continue to require careful discussion with each individual couple before conception.

Journal Article↗

[Diagnostic tools in inflammatory bowel diseases].

The two major inflammatory bowel diseases, Crohn's disease (CD) and ulcerative colitis (UC), represent clinicopathologic entities that traditionally have been diagnosed on the basis of a combination of clinical, radiologic, endoscopic, and histologic features. The presence of an inflammatory syndrome associated with typical clinical manifestations must lead to perform endoscopic examinations. Ileocolonoscopy plays an integral role in establishing the diagnosis, excluding other etiologies, distinguishing Crohn's disease from ulcerative colitis, defining the patterns, extent, and activity of mucosal inflammation, and obtaining mucosal tissue for histologic evaluation of inflammatory bowel disease. Small bowel follow through is still a major examination. However, the role of CT and MRI (using enteroclysis) in the imaging of inflammatory bowel disease has also increased in importance. Capsule endoscopy could be a valuable diagnostic tool in patients with suspected Crohn's disease that has not been confirmed using standard imaging techniques. Serum perinuclear antineutrophil cytoplasmic antibodies (pANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) have recently been added to our diagnostic armamentarium. Serology may prove to be useful in predicting the evolution of indeterminate colitis. Substantial progress could come from the improving of serologic and genetic tests in the future.

Antibodies, Antineutrophil Cytoplasmic↗

Radiologic-pathologic correlation of inflammatory bowel disease.

The various inflammatory bowel diseases produce a wide spectrum of mucosal and bowel wall changes. No one radiolographic sign, or even combination of signs, is completely pathognomonic. A consideration of the pathophysiology responsible for the radiographic findings is helpful as an aid to understanding and to limit reliance upon matching of nonspecific signs with specific diagnosis. Patterns of mucosal ulceration, polyp formation, and strictures in the common superficial and transmural inflammatory diseases are emphasized.

Colitis, Ulcerative↗

The attitude of employers to people with inflammatory bowel disease.

Many patients with inflammatory bowel disease are anxious about their future prospects of employment. Personnel managers at 61 major national and 136 principal local employers in Leicester and Cardiff were asked to provide details about their attitude to people with inflammatory bowel disease and the type of health care they offer to employees. Over one million people were employed by these companies. A poor response rate of 27% suggested at best disinterest in the subject on the part of employers. In those who did reply the attitude to people with inflammatory bowel disease was often positive, although up to a quarter (25%) would not continue to employ people if they developed these conditions and many (30%) would not provide time off work to attend hospital clinics. Only 60% of respondents would consider providing lighter duties to affected employees. In general there is a surprisingly negative attitude to promotion of people with chronic diseases such as epilepsy, multiple sclerosis or liver disease. This seems less so in inflammatory bowel disease.

Attitude to Health↗

Serum interleukin-6 is related to disease activity but not disease specificity in inflammatory bowel disease.

Interleukin-6 (IL-6) has a major function in the regulation of the inflammatory process. We aimed to define its role as a parameter of disease activity and extent in inflammatory bowel disease. Serum concentrations of IL-6 were measured in 28 patients with Crohn's disease (CD) and in 15 with ulcerative colitis (UC) before starting corticosteroid treatment. Disease activity was measured by standard activity indexes. Serum IL-6 levels were increased in patients with CD (36 +/- 8 pg/ml; p < 0.001) and UC (10 +/- 4 pg/ml; p < 0.05) as compared with 25 control patients. A significant correlation between serum IL-6 concentrations and disease activity was found in patients with CD as well as in patients with UC (active CD: 73 +/- 14 pg/ml, inactive disease: < 10 pg/ml, p = 0.003; active UC: 26 +/- 10 pg/ml, inactive disease: < 10 pg/ml, p = 0.004). IL-6 serum levels were related to the acute-phase reactant c-reactive protein (r = 0.51, p < 0.01) in CD patients. The serum IL-6 concentrations were more pronounced in CD of the colon than in disease limited to the small bowel (p < 0.05). In patients with CD as well as in patients with UC, IL-6 serum concentrations showed a higher sensitivity for disease activity (94 and 83%) than serum c-reactive protein levels. In patients without corticosteroid treatment, the IL-6 serum concentration is related to disease activity in CD as well as UC. Serum IL-6 levels show a higher correlation with disease activity than c-reactive protein levels.

Adult↗

Metabolic Bone Disease in Inflammatory Bowel Disease.

An oral calcium supplement (1000 mg/day) is recommended. Regular exercise should be performed. Ethanol intake should be moderate. Protein intake should be moderate. The patient's vitamin D status should be determined and corrected with an oral supplement when deficiency is present. Baseline and yearly bone density measurement should be taken. Alendronate, 10 mg/d orally, or risedronate, 5 mg/d orally, should be given to patients with osteopenia. Use of corticosteroids, cyclosporin, tacrolimus, and methotrexate should be limited to the short term when possible. Estrogen replacement therapy is recommended in postmenopausal women unless contraindications exist.

Journal Article↗

Urinary excretion of N-methylhistamine as a marker of disease activity in inflammatory bowel disease.

OBJECTIVE: Mast cells are thought to participate in the pathogenesis of inflammatory bowel disease (IBD). In this study, urinary excretion of N-methylhistamine (UMH), a stable metabolite of the mast cell mediator histamine, was evaluated as an indicator of disease activity in patients with IBD. METHODS: Urinary excretion of UMH (microg/mmol creatinine x m2 body surface area) was measured by radioimmunoassay in 55 controls, 56 patients with Crohn's disease, and in 36 patients with ulcerative colitis. Excretion rates were correlated with clinical, serological, and endoscopic disease activity, disease extent, and location. RESULTS: Urinary excretion of UMH was found to be significantly elevated in IBD. Patients with active Crohn's disease (7.1 +/- 4.2, p = 0.002 vs controls) and active ulcerative colitis (8.1 +/- 4.8, p = 0.02 vs controls) had higher rates of UMH excretion than patients in remission (6.3 +/- 3.8 and 5.2 +/- 2.3, respectively) or controls (4.6 +/- 1.9). In Crohn's disease and ulcerative colitis, a significant correlation of UMH excretion with clinical disease activity was obtained (Crohn's Disease Activity Index r2 = 0.58, Clinical Activity Index r2 = 0.57, p < 0.0001). Serologically, orosomucoid showed the best positive correlation with disease activity (Crohn's Disease Activity Index r2 0.80, Clinical Activity Index r2 = 0.86, p < 0.0001), but UMH excretion was found to reflect disease activity more accurately than C-reactive protein (Crohn's Disease Activity Index r2 = 0.46, Clinical Activity Index r2 = 0.42, p < 0.0001). No association between UMH excretion and disease type or localization could be found in Crohn's disease. However, UMH excretion correlated strongly with endoscopic severity of inflammation in Crohn's disease (Crohn's Disease Endoscopic Index of Severity r2 = 0.70, p < 0.0001) or disease extent in ulcerative colitis. CONCLUSIONS: Urinary excretion of the histamine metabolite UMH is enhanced in IBD. It appears to represent an integrative parameter to monitor clinical and endoscopic disease activity in IBD, which appears to be influenced most likely by mediators released from histamine-containing cells, such as intestinal mast cell subtypes.

Adolescent↗

Management of inflammatory bowel disease.

Patients with an inflammatory bowel disease, such as ulcerative colitis or Crohn's disease, have recurrent symptoms with considerable morbidity. Patient involvement and education are necessary components of effective management. Mild disease requires only symptomatic relief and dietary manipulation. Mild to moderate disease can be managed with 5-aminosalicylic acid compounds, including olsalazine and mesalamine. Mesalamine enemas and suppositories are useful in treating proctosigmoiditis. Antibiotics such as metronidazole may be required in patients with Crohn's disease. Corticosteroids are beneficial in patients with more severe symptoms, but side effects limit their use, particularly for chronic therapy. Immunosuppressant therapy may be considered in patients with refractory disease that is not amenable to surgery. Inflammatory bowel disease in pregnant women can be managed with 5-aminosalicylic acid compounds and corticosteroids. Since longstanding inflammatory bowel disease (especially ulcerative colitis) is associated with an increased risk of colon cancer, periodic colonoscopy is warranted.

Adrenal Cortex Hormones↗

Is there any food I can eat? Living with inflammatory bowel disease and/or irritable bowel syndrome.

INTRODUCTION: Inflammatory bowel disease (Crohn's disease and ulcerative colitis) and irritable bowel syndrome are chronic, debilitating gastrointestinal (GI) disorders. There are no known causes of inflammatory bowel disease and/or irritable bowel syndrome. Both of these GI conditions significantly impair quality of life and the ability to complete activities of daily living. Unfortunately, there has been little education and research surrounding the evaluation of effective coping strategies with respect to GI disorders, particularly from the perspective of those diagnosed. As such, exploring the strategies of individuals with GI disorders would provide information concerning coping strategies from the perspective of those afflicted. PURPOSE: The overall objective of this research was to explore the lived experience of women who had been diagnosed with inflammatory bowel disease and/or irritable bowel syndrome. This article specifically explores the relationship between food and irritable bowel syndrome and/or inflammatory bowel disease. METHODS: Eight females, diagnosed with inflammatory bowel disease and/or irritable bowel syndrome, were recruited via on-campus posters from a university in southern Ontario, Canada. Qualitative information was collected in the form of background questionnaires, e-mail interviews, and face-to-face interviews, which were subsequently analyzed for trends. RESULTS: Every woman reported that one of the most significant means by which to cope with their condition centered around food consumption or controlling their food consumption. Subjects identified the importance of determining their "trigger foods," selecting healthy food choices, the impact of stress, and problems associated with food and travel. CONCLUSIONS: This research, predicated on the narratives of women diagnosed with GI disorders, substantiates the profound effect that food has on conditions of the GI tract. All of the women identified their relationship with food as a dynamic learning process, one that they thought would be a lifelong struggle. The implications for community health nurses in assisting individuals with GI disorders are discussed.

Activities of Daily Living↗

The role of breastfeeding in postpartum disease activity in women with inflammatory bowel disease.

BACKGROUND: Women with inflammatory bowel disease (IBD) have an increased risk of experiencing a flare in the postpartum period. Work in other autoimmune disorders has found that breastfeeding may be associated with an increased risk for developing postpartum disease relapse. AIM: To assess the association between breastfeeding behavior and postpartum disease activity. METHODS: Women with IBD followed at a tertiary care center with a history of childbirth within the past 5 yr were recruited. Medical records were reviewed for disease type, disease activity during and after pregnancy, medication use, smoking, and breastfeeding behavior. The exposure of interest was breastfeeding prior to the onset of disease activity following a successful asymptomatic pregnancy. RESULTS: One hundred and twenty-two consecutive women who fit eligibility criteria were studied. Overall, only 44% (54/122) of the women had breastfed their infant. Reasons included physician recommendation, fear of medication interactions, and personal choice. Forty-three percent (23/54) of those who breastfed experienced a postpartum flare of their disease. The unadjusted odds ratio for disease activity with a history of breastfeeding was 2.2 (95% CI 1.2-3.9, p= 0.004). When stratified by disease type, the OR for ulcerative colitis was 0.89 (0.29-2.7, p > 0.05) and Crohn's disease 3.8 (1.9-7.4, p < 0.05). When adjusted for medication cessation, the OR became nonsignificant. CONCLUSIONS: A significant number of women with IBD do not breastfeed their children. Any relationship between breastfeeding and disease activity may be more a consequence of discontinuation of IBD therapies.

Adult↗

Physiological basis for novel drug therapies used to treat the inflammatory bowel diseases. I. Immunology and therapeutic potential of antiadhesion molecule therapy in inflammatory bowel disease.

Adhesion molecules regulate the influx of leukocytes in normal and inflamed gut. They are also involved in local lymphocyte stimulation and antigen presentation within the intestinal mucosa. In intestinal inflammation, many adhesion molecules are upregulated, but alpha4-integrins most likely hold a key position in directing leukocytes into the inflamed bowel wall. Therapeutic compounds directed against trafficking of leukocytes have been designed and are being developed as a novel class of drugs in the treatment of Crohn's disease and ulcerative colitis. This review deals with the immunological aspects of leukocyte trafficking focused on gut homing of T cells. Second, the changes in adhesion molecules and T cell trafficking during intestinal inflammation are discussed. Finally, we review the clinical data that have been gathered with respect to the therapeutic potential and the safety of antiadhesion molecule treatment. Antegren, or natalizumab, a humanized anti-alpha4 integrin IgG4 antibody, has been most extensively evaluated and may be close to registration. A more specific humanized alpha4beta7-integrin MLN-02 has shown preliminary clinical efficacy in ulcerative colitis, and both antergren and MLN-02 appear to be very safe. Trials with the anti-ICAM-1 antisense oligonucleotide ISIS-2302 in steroid refractory Crohn's disease have provided conflicting efficacy data. In the near future, some of these novel biological agents may prove valuable therapeutic tools in the management of refractory inflammatory bowel disease, although it is too early to define the patient population that will benefit most from these agents.

Antibodies, Monoclonal↗

Is it possible to assess disease activity of inflammatory bowel disease with scintigraphy?

99mTc-HMPAO-leukocyte scintigrams were compared with the activity index (AI) of Van Hees in 145 inflammatory bowel disease (IBD) patients. Labelling of leukocytes with 99mTc-HMPAO was less time-consuming and less laborious than 111In-labelling of granulocytes; in addition, the radiation dose for the patient is lower and the shorter acquisition time allows multiple views. In a previous comparative study 99mTc-leukocytes proved superior to 111In-granulocytes in detecting active IBD. The present study shows that a positive AI (> 125) is associated with a positive 99mTc-leukocyte scintigram (40 pts); a negative 99mTc-leukocyte scintigram is only found in patients with a negative AI (27 pts). In 30 out of 78 patients with an AI < or = 125 and a positive scintigram these positive results were confirmed by radiological and/or endoscopic examinations, but in the remaining 48 patients verification of the scintigraphic result was prohibited due to the absence of other confirmative examinations within 1 month of scintigraphy. In our view 99mTc-leukocyte scintigraphy may well be the gold standard for functional assessment of inflammation intensity and localization in IBD patients.

Granulocytes↗

Colo-rectal biopsy in inflammatory bowel disease.

The term inflammatory bowel disease (IBD) is viewed as all-inclusive, covering the full panoply of intestinal disorders in which inflammatory changes are a prominent feature, including those of infectious, toxic, and intrinsic origin as well as the idiopathic entities ulcerative colitis and Crohn's disease. This chapter describes and discusses those aspects of colo-rectal biopsy in IBD which can help pathologists make optimal interpretations. The areas covered are: 1) methods used to prepare biopsy specimens for study, 2) normal histologic findings and common artefacts, 3) basic pathologic changes occurring in IBD, 4) a general approach to differential diagnosis in IBD, and 5) discussion of the various individual forms of IBD. The importance of full and reliable information exchange between the endoscopist and pathologist is stressed. Special attention is given to features in biopsy specimens which help in differentiating between ulcerative colitis and Crohn's disease. Other entities discussed are bacterial dysenteries; gonococcal proctitis; tuberculosis; Whipple's disease; amebiasis; balantidiasis; schistosomiasis; cryptosporidiosis; lymphopathia venereum; cytomegalovirus infection; histoplasmosis; antibiotic colitis; IBD due to cytotoxic drugs (5-FU), heavy metals, and foodstuffs; irradiation colitis; ischemic colitis; solitary ulcer syndrome; diverticulitis; and colitis secondary to obstruction. The term pseudomembranous enterocolitis is also considered.

Biopsy↗