Martin J. Wagtmans

Crohn's disease in the elderly : A comparison with young adults

We compare the clinicopathological features of 98 Crohns disease (CD) patients with initial symptoms at 40 years of age or older (elderly; male n = 56, female n = 42) with those of 347 CD patients with onset of symptoms between the age of 16 and 40 years (young adults; male n = 166, female n = 181). The frequency of presenting symptoms, such as diarrhea, rectal blood loss, and weight loss were comparable in both groups, except for abdominal pain/cramps, which occurred somewhat less frequently in the elderly (59% vs. 71%, p < 0.05). The mean lag time between onset of symptoms and first visit to a general practitioner (GP) was considerably shorter in the elderly than in the young adults (0.2 years vs. 0.6 years, p < 0.001), as was the lag time between GP and referral to a specialist (0.6 years vs. 1.0 years, p < 0.07). Overall, this resulted in a significantly (p < 0.01) shorter time to establish the diagnosis in the elderly (1.8 years vs. 2.7 years). Crohns disease as correct initial diagnosis was in the elderly less frequently observed than in the young adults (49% vs. 61%, p < 0.05), in contrast to diverticulitis (7.1% vs. 0%) and malignancy (6.1% vs. 0.9%), which were more frequently encountered as incorrect preliminary diagnosis in the elderly (both p < 0.005). The percentage of patients who underwent an abdominal operation was similar in both groups (83% vs. 77%), but the diagnosis CD was in the elderly more frequently established at first operation than in young adults (25% and 12%, p < 0.005). The elderly were found to undergo a bowel operation or resection earlier after onset of symptoms. The development of recurrence after bowel resection, although occurring in a lower percentage of patients, was significantly shorter than in the young adults (3.7 years vs. 5.8 years, p < 0.02). Arthritic extraintestinal manifestations were equally frequent in both groups, but elderly patients had significantly less relatives in the first or second degree affected by CD (3.1% vs. 12%, p < 0.02). We conclude that the diagnosis Crohns disease is more readily established in elderly patients. Moreover, these patients less frequently have abdominal pain/cramps as a presenting symptom, a shorter time interval between onset of symptoms and first resection, and subsequent recurrence of the disease. In addition, elderly CD patients have less relatives affected by the same disease. Thus, CD in the elderly appears to be characterized by a more rapid development.

Crohn's disease of the upper gastrointestinal tract

Although Crohns disease (CD) is generally found in the ileum and/or colon, since the 1960s it has become evident that this chronic inflammatory disorder of unknown aetiology can affect the whole gastrointestinal tract from mouth to anus. In 0.5-13% of patients with ileocolonic CD the disease occurs in the upper gastrointestinal tract as well (i.e., from mouth through jejunum). With the radiological double-contrast technique, however, early signs of upper gastrointestinal CD may be detected in 20-40% of patients with ileocolitis. On the other hand, histologically evaluated biopsies from the lower oesophagus, body of the stomach, gastric antrum and the duodenal bulb of patients with Crohns disease from whom the upper gastrointestinal tract is normal, according to X-ray or endoscopy may reveal lesions, which are considered to be pathologically diagnostic. Jejunal involvement occurs in 4-10% of patients with ileitis, ileocolitis or colitis. In early studies biopsies of apparently normal buccal mucosa from patients with Crohns disease showed a significant correlation between the activity of the disease, as defined by the Crohns Disease Activity Index, and the number of plasma cells containing IgM, suggesting a generalized activated humoral defence system during relapse. A diagnosis of Crohns disease of the upper gastrointestinal tract can be achieved by combining recognition of clinical, roentgenographic, and endoscopic features. Provided that other causes of granulomatous involvement of the gastrointestinal tract can be excluded, non-caseating granulomas are generally accepted as the histological proof of Crohns disease. When Crohns disease does involve the upper gastrointestinal tract, there is nearly always concomitant disease in the small bowel or colon. Compared to patients with an ileocolonic localization, patients with Crohns disease in the upper gastrointestinal tract more frequently have colic-like abdominal pain and/or cramps, nausea and anorexia as presenting symptoms and are younger at onset of the disease. Medical therapeutic principles are the same as for Crohns disease elsewhere in the gastrointestinal tract. Absolute indications for surgical treatment are massive bleeding, progressive stenosis, and extensive fistula formation.

Proximal Crohn's disease: review of the clinicopathologic features and therapy.

Crohns disease in the proximal region of the digestive tract is uncommon. Better diagnostically procedures and more careful histologic examination has led to a higher detection of proximal Crohns disease. The diagnosis is based on symptoms, endoscopy with serial sections, or double contrast radiography. The most common histologic finding for this diagnosis are granulomas in the mucosa in Helicobacter pylori-negative patients, but the granulomas are not always frequently detected. Endoscopic lesions in the proximal regions look like the lesions that could be found in the distal regions. Notching in the duodenal folds could be a strong indication for Crohns desease. Radiological lesions are not always characteristic, but should be used in combination with endoscopy. Stenosis is an important complication, but fistula formation and pseudodiverticular formation is possible. There is no uniform medical therapy, but the regular anti-inflammatory management for Crohns disease is most often used. Sometimes surgery is needed.

Gender-related differences in the clinical course of Crohn’s disease

OBJECTIVE:The aim of this study was to analyze the clinical and epidemiological differences between women and men affected by Crohns disease.METHODS:The clinical course of 275 female Crohns disease patients was compared with that of 266 male patients.RESULTS:Mean age at onset of symptoms and at diagnosis was 25.7 yr versus 27.7 yr and 28.8 yr versus 30.7 yr in women and men, respectively. Mean lag-time between onset of symptoms and establishment of the diagnosis were similar in both groups, without differences in presenting symptoms and initial localization of lesions. In women, however, some extraintestinal manifestations of Crohns disease were found to occur more often. The percentage of patients who underwent an abdominal operation was quite similar in both groups (81% vs 77%). Mean lag-time between onset of symptoms and first bowel resection was not different. However, the lag-time between bowel resection and recurrence of disease was significantly shorter in women than in men (respectively, 4.8 yr vs 6.5 yr, p = 0.04), particularly regarding primary ileocecal resections. Overall, ileocecal resections were significantly more frequently performed in female than male patients (44% and 32%, respectively, p = 0.004). Female patients were also found to have significantly more often relatives in the first or second degree affected by Crohns disease than male patients (15% vs 8.3%, p = 0.02).CONCLUSIONS:Extraintestinal manifestations occur more often in female Crohns disease patients than in male patients. Furthermore, an ileocecal resection, which is accompanied by an earlier recurrence, is more often performed in female than in male patients. Female patients have more often relatives with the same disease.

Effect of cortisol and ACTH on corticosteroid-suppressed peripheral blood natural killer cells from healthy volunteers and patients with Crohn's disease.

Recently, we have shown that administration of adrenocorticotropic hormone (ACTH) to corticosteroid-treated Crohns disease (CD) patients increased the peripheral blood natural killer (NK) cell activity which was suppressed by the corticosteroids. To elucidate this observation we analysed the in vitro effect of budesonide, prednisolone, cortisol, and ACTH on NK cells of healthy volunteers and corticosteroid-treated CD patients. Incubation of peripheral blood mononuclear cells (PBMNC) from healthy volunteers during the cytotoxicity assay caused a dose-dependent inhibition of NK cell activity by the three corticosteroids, while ACTH had hardly any effect. Pre-incubation for 18 h with high and low inhibiting concentrations also showed a significant inhibiting effect on NK cell activity of the corticosteroids. The percentage of CD56+ NK cells tended to increase after pre-incubation with a high inhibiting concentration of budesonide, prednisolone, and cortisol. Incubation of budesonide- or prednisolone-suppressed PBMNC from healthy volunteers and CD patients, with ACTH and/or cortisol, to mimic the in vivo situation, did not restore the corticosteroid-induced suppression of NK cell activity. The increase of the budesonide- or prednisolone-suppressed NK cell activity after in vivo administration of ACTH to the CD patients is therefore probably not a direct effect of cortisol or ACTH. Presumably other factors like cytokines and/or neurohormones must be involved in the in vivo interaction between corticosteroids, ACTH, and NK cells.

Budesonide in inflammatory bowel disease

Due to its immunomodulatory and anti-inflammatory properties glucocorticosteroids have proved to be highly efficacious in patients with inflammatory bowel disease. However, because of the risk of side-effects, the dose and duration of therapy with systemically acting glucocorticosteroids have to be restricted. Recently the use of topically acting glucocorticosteroids has attracted great interest. Among the various topically acting glucocorticosteroids budesonide has emerged as the most promising. Budesonide is highly potent, is readily water-soluble and has low systemic bioavailability, thus reducing the risk of corticosteroid-related side-effects. When given as enema to patients with proctitis or proctosigmoiditis, the efficacy of budesonide is greater than that of placebo and equal to that of prednisolone or 5-aminosalicylic acid enemas. In an enteric-coated formulation budesonide is more effective than placebo in achieving and maintaining remission in patients with ileocecal Crohns disease. Although corticosteroid-related side-effects are rare, some suppression of the hypothalamic-pituitary-adrenal axis may occur.