Epidemiological study on the incidence of inflammatory bowel disease in 4 Spanish areas. Spanish Group on the Epidemiological Study of Inflammatory Bowel Disease

BACKGROUND: The incidence of inflammatory bowel disease (IBD) shows marked geographical variations. The aim of this study was to determine and compare the incidence of IBD in four Spanish areas: Sabadell (Northeast), Vigo (Northwest), Mallorca island and Motril (South). PATIENTS AND METHODS: Prospective survey based on inception cohorts over a two-years period (1 October 1991 to September 1993). Subjects were the patients resident in these areas and diagnosed of IBD according to a standard protocol for case ascertainment and definition. RESULTS: Altogether 328 cases were identified, of whom 191 were diagnosed as ulcerative colitis (UC), 135 as Crohn's disease (CD) and 2 as indeterminate colitis. The overall adjusted incidence rate per 100,000 persons between ages 15-64 years of UC and CD were respectively 9.8 and 5.2 in Sabadell, 7.7 and 5.0 in Vigo, 7.8 and 5.8 in Mallorca and 4.3 and 6.5 in Motril. The Incidence rate ratio showed no significant differences for either conditions among these areas. The global adjusted incidence rate of UC in Spanish areas (8.0; IC 95%: 6.3-9.7) was significantly lower to that of Northern European countries while that of CD (5.5; IC 95%: 4.1-6.9) was between that of Northern and Southern Europe with no significant differences. CONCLUSIONS: The incidence of IBD did not show differences among the Spanish areas, and rates are between 2 and 6 times higher than those previously reported. The incidence of UC is significantly lower than that observed in the North of Europe, while for CD the incidence is between that of Northern and Southern Europe.     

CD4+ T-cell population mediates development of inflammatory bowel disease in T-cell receptor alpha chain-deficient mice

BACKGROUND & AIMS: Increase of T cells expressing CD4 and T-cell receptor (TCR) alpha- beta+ (beta[dim]) was observed in the mucosal and peripheral lymphoid tissues of TCR alpha-/- mice with inflammatory bowel disease (IBD). The aim of this study was to characterize the CD4+ TCR alpha-beta+ T cells. METHODS: Cytokine production, TCR V beta usage, and helper function for Peyer's patch B cells by the CD4+ TCR alpha-beta+ T cells were assessed. RESULTS: The CD4+ TCR alpha-beta+ T cells purified from mesenteric lymph nodes and lamina propria of the intestine of IBD mice exclusively produced interleukin 4, used selected subsets (V beta6, V beta8, V beta14, and V beta15) of TCR, and massively proliferated after stimulation with staphylococcal enterotoxin B. Addition of the CD4+ TCR alpha-beta+ T cells to Peyer's patch B-cell cultures markedly enhanced immunoglobulin (Ig) A, IgG, and IgM antibody responses. Furthermore, depletion of the TCR alpha-beta+ T cells with monoclonal antibody against TCR beta chain completely suppressed the onset of IBD and polyclonal B-cell activation in the TCR alpha-/- mice. CONCLUSIONS: These findings suggest the CD4+ TCR alpha-beta+ T cells-mediated development of IBD in TCR alpha-/- mice.     

Predictors of health care utilization in patients with inflammatory bowel disease: a longitudinal study

OBJECTIVE: To study the changes in normal sexual behavior that accompany the vulvar vestibulitis syndrome and to gauge an appropriate classification for the resulting sexual dysfunction. STUDY DESIGN: Following full medical screening, questionnaires were administered to assess sexual history, illness behavior and vulvar discomfort. Forty patients who met the criteria of vestibulitis syndrome composed the study cohort. RESULTS: The average duration of reported vulvar pain was 33 months (range, 3-240). The cohort showed no significant differences when compared with normative data on the sexual history form in their level of sexual desire, duration of intercourse or chance of female orgasm with intercourse or masturbation. Patients were: (1) highly likely to experience vulvar pain with intercourse (P < .001), (2) highly likely to have significantly reduced arousal potential (P < .001), (3) highly likely to complain of vulvar symptoms preventing intercourse from occurring (P < .001), (4) highly likely to have a reduced interest in intercourse and to have negative feelings toward it (P < .001); and (5) highly likely to refuse a partner's sexual advances (P < .001). CONCLUSION: In the case of vulvar vestibulitis, the most appropriate Diagnostic and Statistical Manual of Mental Disorders, fourth edition, classification appears to be sexual dysfunction due to a general medical condition.     

Cardiovascular abnormalities in Kawasaki disease. An Italian prospective study

We report a prospective study performed over a 9 year period in 96 children with Kawasaki disease (mean age 35 +/- 29 months), 84 of whom < 5 years of age. The male/female ratio was 1.5 (57/39). A total of 38 patients had cardiac involvement, including flattened T waves in the ECG (10 patients), pericardial effusion (6 patients), myocarditis (1 patient), and coronary artery aneurysms (25 patients; frequency of aneurysms: 26%). All patients were evaluated during the acute phase (first month) of the illness. The first echocardiographic examination was performed 15 days (range 4.30 days) from the appearance of fever, and coronary aneurysms were observed in 23 patients; in 2 patients, however, aneurysms appeared later (2 and 6 months). Aneurysms were small (< or = 4.5 mm) in 12, medium (4.5-7 mm) in 11, and large (> 7 mm) in 12 patients. Male sex (p = 0.02), age < 12 months (p = 0.005), ESR (p = 0.001), platelet count (p = 0.009), and pericardial effusion (p = 0.02) were significantly related to the presence of aneurysm. Among females, incidence of aneurysms was significantly higher in infants < 12 months than in older patients (60 vs 6%, p < 0.001). Intravenous immunoglobulin treatment was started early (within 10 days) in 61 patients and late (> 10 days) in 22. Compared to late treatment, early i.v. immunoglobulin treatment was associated with smaller aneurysms and higher regression rate (67 vs 28%, p < 0.05). No difference was observed concerning frequency and number of dilated vessels as related to therapeutical regimens. Total i.v. immunoglobulin dose (2 g/kg) was administered over 1-2 days in 26 patients (scheme I) or over 4-5 days in 58 (scheme II). Frequency of aneurysms was significantly lower in patients treated early (p = 0.02). No myocardial infarctions or deaths occurred at short- or long-term follow-up.     

The menstrual cycle and its effect on inflammatory bowel disease and irritable bowel syndrome: a prevalence study

OBJECTIVE: Female patients with bowel disease commonly report worsening symptoms in relation to the menstrual cycle. Our aim was to determine the nature of gastrointestinal symptoms correlating with the menstrual cycle in women with inflammatory and irritable bowel disease. METHODS: This was a retrospective study involving 49 women with ulcerative colitis (UC), 49 women with Crohn's disease (CD), 46 women with irritable bowel syndrome (IBS), and 90 healthy community controls. Participants were interviewed using a questionnaire including information regarding general health, medication history, pregnancy, as well as premenstrual and menstrual symptoms. Chi2 testing and logistic regression modeling were used to test for differences in frequencies between groups and for risk analysis. RESULTS: Premenstrual symptoms were reported by 93% of all women but statistically more often by patients with CD (p < 0.01). CD patients were also more likely to report increased gastrointestinal symptoms during menstruation ( < 0.01), diarrhea being the symptom reported most often. All disease groups had a cyclical pattern to their bowel habits significantly more than controls (p=0.01). Cyclical symptoms included diarrhea, abdominal pain, and constipation. Logistic regression revealed an odds ratio (OR) of 1.1 (95% CI 0.9-1.2) for experiencing bowel symptoms during the premenstrual and menstrual phases and an OR of 2.0 (95% CI 1.2-3.2) for experiencing a cyclical pattern in bowel habit changes in women with bowel disease. CONCLUSION: The prevalence of menstrually related symptoms is high, and appears to affect bowel patterns. The physiological and clinical effects of the menstrual cycle should be taken into consideration when assessing for disease activity.     

Prevalence of serious eye disease and visual impairment in a north London population: population based, cross sectional study

OBJECTIVE: To estimate the magnitude of serious eye disorders and of visual impairment in a defined elderly population of a typical metropolitan area in England, and to assess the frequency they were in touch with, or known to, the eye care services. DESIGN: Cross sectional survey using two stage cluster random sampling. SETTING: General practices in north London. SUBJECTS: Random sample of people aged 65 and older, drawn from a defined population of elderly people registered with 17 general practice groups. MAIN OUTCOME MEASURES: Proportions and population prevalence estimates were determined for visual acuity, assessed with the person's own spectacles (if any), classified into four categories: prevalence of cataract, age related macular degeneration, and refractive error causing visual impairment and of definite primary open angle glaucoma; and status of contact with eye services. RESULTS: 1547 of 1840 (84%) eligible people were examined. The population prevalence of bilateral visual impairment (visual acuity <6/12) was 30%, of which 72% was potentially remediable. 92 of these 448 cases (21%) had visual acuity <6/60 ("blindness") in one or both eyes. Prevalence of cataract causing visual impairment was 30%; 88% of these people were not in touch with the eye services. The prevalence of vision impairing, age related macular degeneration was 8% and of glaucoma (definite cases) was 3%. Three quarters of the people with definite glaucoma were not known to the eye services. CONCLUSIONS: Untreated visual impairment and eye disorders affect a substantial proportion of people aged 65 years and older. These findings should contribute to the setting up of future strategies for preservation of sight and eye health services in general.     

Laparoscopic-assisted bowel resections in inflammatory bowel disease: state of the art

The objectives of this paper are to review the rational, the present results and future of laparoscopic-assisted bowel surgery in patients with inflammatory bowel disease (IBD). Only a few centres in the world report on laparoscopic bowel resection in IBD that include stoma surgery, ileocolic resection, left, right and (sub)total colectomy for Crohn's disease, and subtotal or restorative total proctocolectomy (ileal pouch anal procedures). The combined series report conversion rates between 2.5% and 22.2%. Ileocolic resection, stoma creation, stricturoplasty and segmental small bowel resection are associated with an acceptable length of surgery, but laparoscopic(-assisted) total colectomy or restorative proctocolectomy still demand up to 4-6 hours of operative time. The few randomised studies addressing laparoscopic-assisted (segmental) bowel surgery versus conventional surgery demonstrated significantly less pain, a quicker return to self-care and a shorter hospital stay. The results of the series reporting on laparoscopic-assisted (ileo)colectomy in IBD are similar to those from these randomised studies. Laparoscopic-assisted subtotal colectomy and restorative proctocolectomy have no benefit compared with conventional surgery other than superior cosmesis. Morbidity of laparoscopic (ileo)colectomy in IBD is low, that of laparoscopic-assisted subtotal colectomy and restorative proctocolectomy remains to be seen. The various laparoscopic bowel resections done in IBD are all feasible. The first series describing laparoscopic surgery for IBD indicate that laparoscopic-assisted segmental (ileo)colectomy is safe and is the preferred approach provided it is done in a centre specialised in the treatment of IBD and by skilled laparoscopic surgeons beyond the learning curve. Until now, laparoscopic-assisted subtotal colectomy and restorative proctocolectomy do not have the same short-term benefits as seen in other laparoscopic colorectal procedures. Patients with inflammatory bowel disease (IBD) have a high life-time risk of having abdominal surgery and reoperations. The proposed advantages of laparoscopic surgery in this group of young patients might be higher than in patients with other colorectal diseases. Minimal physiologic insult in patients who already are under significant physiologic stress, less adhesion formation and superior cosmesis are important benefits over time. In a time where patient's demands will increase, the future of laparoscopic colonic surgery in IBD looks assured.     

Interleukin-4 hyporesponsiveness in inflammatory bowel disease: immune defect or physiological response?

Data on the relationship between academic performance (grade point average) of college athletes and their perceptions of the effects of anabolic steroids on their sport and their performance were collected from Division 1 athletes (N = 1,638) representing 12 varsity sports chosen from five universities nationwide. The response rate was 74%. Analysis yielded differences between athletes with high and low GPAs in perceptions of the effects of anabolic steroids. The lower the GPA, the less likely the athletes were to believe that anabolic steroids are a threat to health, are a problem in their sport, and are addictive. Also, they were more likely to believe that anabolic steroids enhance performance.     

Thromboembolic complications in inflammatory bowel disease

Thromboembolic complications during the course of inflammatory bowel disease are infrequent but are mainly found in young patients and are associated with a high morbimortality. The etiopathogenesis of these complications has been widely debated and the existence of coagulation alterations and fibrinolysis have been suggested. Nonetheless, the mechanism must be complex since not only do not all the patients with these alterations present this complication but neither do all the patients with thromboembolism have recognized coagulation disorders. The most common clinical presentation is deep vein thrombosis with pulmonary embolism with arterial thrombosis being rare. Five patients with Crohn's disease and two with ulcerative colitis who presented a total of new thromboembolic episodes, six arterial (1 in primitive iliac artery, 1 in common femoral artery, 1 in humeral-axillary artery, 2 in internal carotid and 1 in superior mesenteric artery) and three of venous localization (1 in brachyocephalic-subclavian trunk, 1 axillary and 1 iliac-femoral/pulmonary thromboembolism) are reported. An updated review of the etiopathogenesis, presentation, treatment and prophylaxis of the thromboembolic complications of inflammatory bowel disease is presented.     

Prediction of outcome in neurotic disorder: a 5-year prospective study

BACKGROUND: There have been no previous studies of the outcome of different neurotic disorders in which a prospective group with original randomization to treatment have been followed up over a long period. Such studies are important in identifying the factors associated with good and poor outcome. METHODS: A 5-year follow-up assessment was made of a cohort of 210 psychiatric out-patients seen in general practice psychiatric clinics with a DSM-III diagnosis of generalized anxiety disorder (71), panic disorder (74) or dysthymic disorder (65) and randomized to drug treatment, cognitive and behaviour therapy, and self-help. A total of 182 of the patients (87%) were assessed after 5 years by examination of hospital and GP records using a standardized procedure and outcome determined with a four-point outcome scale. RESULTS: One hundred and seven (60%) of the patients had a favourable outcome but the remainder continued to be handicapped either intermittently or continuously throughout the 5-year period. Analysis of the value of initial data in predicting outcome using polychotomous step-wise logistic regression revealed that five variables were significant predictors of poor prognosis: older age; recurrent episodes; the presence of personality disorder at entry; general neurotic syndrome at entry; and symptom severity after 10 weeks. The initial DSM diagnosis and original treatment given, together with ten other variables, were of no predictive value. CONCLUSIONS: The long-term outcome of neurotic disorder is better predicted by age, personality and recency of onset than by other clinical variables with the exception of initial response to treatment.     

Immunopathogenesis of chronic inflammatory bowel disease

The aetiology and pathogenesis of chronic inflammatory bowel disease are unknown. However, there is circumstantial evidence that immune mechanisms may play a significant role in mediating the gut lesion and various systemic manifestations. The role of the cellular immune system, soluble mediators, including proinflammatory and immunoregulatory cytokines, humoral immunity and mucosal complement activation will be discussed.     

Medical therapy of inflammatory bowel disease

In the past years the advances in therapy of IBD have been characterized mainly by the more widespread use of immunosuppression. Especially azathioprine is currently used in Crohn's disease with methotrexate as the second-line immunosuppressive drug. Cyclosporin may become a drug of choice to treat severe ulcerative colitis but its effect in the long term is probably insufficient. Topically acting glucocorticosteroids have emerged as a valuable safer alternative to standard glucocorticosteroids (GCS) in right ileocolonic Crohn's disease but GCS have no role in maintenance therapy. The most significant development in recent years is the introduction of immunomodulatory treatments using cytokines and anticytokines. The first data show that anti-TNF monoclonal antibodies, especially cA2, not only may result in rapid control of active Crohn's disease but also achieve rapid tissue healing. Repeated administration of cA2 maintains remission. Immunomodulation therapy creates great expectations since early reset of the immunostat might be able to control inflammation in the long term. Safety will be a key issue.     

Surgery for inflammatory bowel disease in Singapore

Inflammatory bowel disease is uncommon in Asians and reports of surgery in these populations are rare. Eighty-two patients with inflammatory bowel disease were seen in the Department of Colorectal Surgery over a five-year period (1989-1994). Twenty-three patients underwent surgery for their disease. There were 12 males and 11 females with 16 Chinese, 4 Indians and 3 Malays. Twelve had Crohn's disease and 11, ulcerative colitis. The majority of patients with Crohn's disease had emergency surgery for bleeding, perforation, abdominal masses and intestinal fistulae. Fifty percent of these had the diagnosis made intraoperatively or post-operatively. Surgery for ulcerative colitis was indicated because of multiple relapses, non-response to medical treatment, side effects of therapy or malignant change. The median age at surgery of patients with Crohn's disease and ulcerative colitis was 39 years (range 24-84) and 40 (range 18-60) respectively. The median follow-up was 22.4 months (range 9-50). The results of surgical therapy in these patients show that surgery when indicated can be done with minimum morbidity and mortality.     

Colorectal cancer in idiopathic inflammatory bowel disease

The development of colorectal cancer is the most serious long-term problem faced by patients with extensive ulcerative colitis and Crohn's colitis, with an incidence 20-fold higher and an average age of onset 20 years younger than colorectal cancer in the general population. This report summarizes the epidemiology, pathology, and recent advances in the molecular pathogenesis of colorectal cancer in inflammatory bowel disease and of its acknowledged precursor, mucosal dysplasia. It also reviews the rationale behind the use of endoscopic surveillance for dysplasia as a means of reducing cancer mortality, as well as some of the issues involved in its effective implementation.     

A prospective 4- to 5-year study of DSM-III-R hypochondriasis

BACKGROUND: Although hypochondriasis is generally thought to be a chronic and stable condition with a relatively low remission rate, this disorder remains understudied. METHODS: This is a 4- to 5-year prospective case-control study of DSM-III-R hypochondriasis. Medical outpatients meeting DSM diagnostic criteria for hypochondriasis completed an extensive research battery assessing hypochondriacal symptoms, medical and psychiatric comorbidity, functional status and role impairment, and medical care. A comparison group of nonhypochondriacal patients from the same setting underwent the same battery. Four to 5 years later, both cohorts were re-interviewed. RESULTS: One hundred twenty hypochondriacal and 133 nonhypochondriacal comparison patients were originally studied. Follow-up was obtained on 73.5% (n = 186) of all patients. At follow-up, the hypochondriacal sample was significantly (P<.001) less hypochondriacal and had less somatization (P<.001) and disability than at inception, but 63.5% (n = 54) still met DSM-III-R diagnostic criteria. When compared with the comparison group using repeated measures multivariate analysis of variance, these changes remained statistically significant (P<.0001). Changes in medical and psychiatric comorbidity did not differ between the 2 groups. When hypochondriacal patients who did and did not meet diagnostic criteria at follow-up were compared, the latter had significantly less disease conviction (P<.05) and somatization (P<.01) at inception, and their incidence of major medical illness during the follow-up period was significantly (P<.05) greater. CONCLUSIONS: Hypochondriacal patients show a considerable decline in symptoms and improvement in role functioning over 4 to 5 years but two thirds of them still meet diagnostic criteria. Hypochondriasis, therefore, carries a very substantial, long-term burden of morbidity, functional impairment, and personal distress.     

Conventional drug therapy in inflammatory bowel disease

The conventional treatment of inflammatory bowel disease should center around the liberal use of one of the many available forms of 5-ASA. Sulfasalazine should be used initially with the newer mesalamine-only containing drugs being reserved for sulfasalazine-intolerant patients or for those patients who require larger doses of medication. The choice of the delivery method should be made with the knowledge of the extent of disease and the potential coverage areas of the individual delivery methods. Systemic and topical glucocorticoids are an invaluable adjunct to 5-ASA therapy, but their use must be directed with the goal of remission induction. The tapering of glucocorticoids should be as prompt as the maintenance of remission allows, with a useful general guideline of decreasing the dose by 1 mg per day. Immunosuppressive therapy, including azathioprine and 6-mercaptopurine, holds promise for refractory cases of inflammatory bowel disease and for their potential steroid sparing properties; antibiotic therapy with metronidazole and ciprofloxacin in the absence of documented infectious disease offers additional routes to control disease. The majority of patients require a combination of drugs to attain remission. Only further study will reveal the ideal regimen for each of the different subsets of inflammatory bowel disease.     

The immune system in inflammatory bowel disease

The activation of naive CD4+ T cells requires two discrete signals: a signal delivered by the T cell receptor following recognition of antigen and an accessory signal transduced when costimulatory receptors interact with their ligands. Particularly important in the development of an immune response to foreign antigens is the T cell molecule CD28, which delivers a potent costimulus when engaged by ligands, B7-1 and B7-2, on antigen-presenting cells. It is interesting that blockade of B7 molecules, which disrupts interactions with CD28 and prevents delivery of the CD28 costimulus, also alters the immune responses to self antigens and prevents the development of clinical disease in murine models of systemic and organ-specific autoimmunity. Herein we review the roles of CD28 and its B7 ligands in the pathogenesis of autoimmunity, discuss efforts to treat animal models of autoimmunity by modifying the CD28 signal, and consider the mechanisms by which manipulation of the CD28 signal alters the course of experimental autoimmune disease.