[Diagnostic image (179). A woman with abdominal pain and weight loss. Intestinal infection with Strongyloides stercoralis]. / Diagnose in beeld (179). Een vrouw met buikpijn en gewichtsverlies. Darminfectie met S. stercoralis.

A 40-year-old woman presented with prolonged abdominal complaints, weight loss and iron deficiency anaemia. Coloscopic biopsy revealed a nematode infestation, probably by Strongyloides stercoralis.

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

Crohn's 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 Crohn's 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 Crohn's 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 Crohn's disease is most often used. Sometimes surgery is needed.

Monitoring response during a randomised controlled trial of escalating interferon dose for chronic hepatitis C infection: predictive value of quantitative and qualitative HCV RNA assays.

BACKGROUND: In chronic hepatitis C infection, raising the interferon dose in initial non-responders may increase the generally poor sustained response rates. Monitoring virological response is essential in this kind of individual patient based approach. Quantitative HCV RNA assays are increasingly used for this purpose. However, their additional value as compared to strictly qualitative HCV RNA assays should be evaluated before they are implemented as a routine measurement, since these assays are more expensive and time consuming than qualitative assays. OBJECTIVES: Goals of this study were (1) to test the hypothesis that increasing interferon dose in initial non-responders results in permanent viral clearance in more patients and (2) evaluation of the predictive value of quantitative versus qualitative HCV RNA assays before and during treatment. STUDY DESIGN: 63 patients were treated in a randomised controlled trial of escalating interferon dose. In the standard treatment group patients received 6 MU alpha-2a thrice weekly for 3 months followed by 3 MU thrice weekly for 3 months. In the experimental group interferon dose was escalated at 6 weeks to 9 MU if HCV RNA was still detectable at 4 weeks. Predictors of response were analyzed at various time points before and during treatment and the predictive value of quantitative HCV RNA measurements was compared to that of qualitative HCV RNA assays. RESULTS: No significant difference in sustained response rate was found between the treatment groups at the end of follow-up. At baseline, the strongest independent predictor for a sustained response was a viral load level below 10(6) copies/ml and age younger than 40 years. During treatment a negative HCV RNA status at week 4 was the strongest predictor of a sustained response. Viral load levels during treatment did not independently predict a sustained response. CONCLUSIONS: While on treatment, qualitative HCV RNA assays should be used to monitor response.

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 Crohn's disease. METHODS: The clinical course of 275 female Crohn's 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 Crohn's 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 Crohn's disease than male patients (15% vs 8.3%, p = 0.02). CONCLUSIONS: Extraintestinal manifestations occur more often in female Crohn's 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.

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

We compare the clinicopathological features of 98 Crohn's 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). Crohn's 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 Crohn's 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.

Clinical aspects of Crohn's disease of the upper gastrointestinal tract: a comparison with distal Crohn's disease.

OBJECTIVE: Our objective was to compare the clinical characteristics of 72 patients with proximal Crohn's disease (PCD), i.e., from mouth through jejunum, with those of 242 patients with distal Crohn's disease (DCD), i.e., from ileum through rectum. METHODS: The diagnosis of Crohn's disease was made on established criteria, e.g., radiology, histology, etc. RESULTS: All but one patient with PCD eventually had DCD as well. Twenty-seven of the 72 patients in the PCD group had manifest PCD at the time of diagnosis. For the 45 PCD patients who, at first, had only distal lesions, 5.0 +/- 4.2 yr passed before a proximal localization was detected. After the diagnosis had been established, the average follow-up time was 19.2 yr in the PCD group and 23.1 yr in the DCD group. The age at onset of disease was significantly (p < 0.01) lower in the PCD group (19.1 yr) than in the DCD group (24.3 yr). However, the time from onset of first symptoms to diagnosis was almost identical in the two groups (PCD group 3.8 yr vs. DCD group 3.4 yr). When complaints began in 1970 or later, after introduction of the flexible endoscope, there was a significant difference between length of time-to-diagnosis in the PCD and DCD groups, i.e., 2.7 and 1.6 yr, respectively, (p < 0.05). Remarkable differences were found in initial symptoms at the onset of disease. Abdominal pain and/or cramps and general malaise were found more often in patients with PCD (respectively, 82% and 21%) than in patients with DCD (respectively, 70% and 10%) (both p < or = 0.05). Although small-bowel resections were performed comparably often in the two groups, in the PCD group, the average length of resected small bowel was significantly greater (77.3 cm, p < 0.002) (n = 53) than in the DCD group (48.1 cm, n = 165). CONCLUSIONS: We conclude that PCD differs from DCD in its clinical presentation, particularly with regard to abdominal pain and/or cramps and general malaise. Patients with PCD are younger at the onset of symptoms, at diagnosis, and when the first abdominal operation is performed, but there is no difference in lag times compared with those of DCD patients. During the course of the illness, more small bowel is resected from PCD patients.

Low seroprevalence of Helicobacter pylori antibodies in historical sera of patients with Crohn's disease.

BACKGROUND: Our aim was to determine the seroprevalence of Helicobacter pylori antibodies in historical sera from a large group of patients with Crohn's disease and to compare the findings with those of a control group of healthy blood transfusion donors. METHODS: The historical sera from 386 patients with Crohn's disease were studied (serum age, 9.9 years; range, 0.4-21.6 years). Serum IgG and IgA H. pylori antibodies were measured with enzyme-linked immunosorbent assay. Western blots (detecting IgG only) were also used to study a subpopulation of the patients' sera and to assess the presence of cagA bands, indicating a cytotoxic variety of H. pylori. The serology of the Crohn's disease patients was compared with that of 277 age-matched controls. A longitudinal follow-up study of 14 IgG and IgA anti-H. pylori-positive and 14 IgG- and IgA-negative Crohn's disease patients was also performed (mean follow-up, 7.6 years; range, 1.7-20.5 years). RESULTS: Of the total Crohn's disease patients, 47 (12.2%) had IgG antibodies against H. pylori, 67 (17.4%) had IgA antibodies, and 31 (8.0%) had both IgG and IgA antibodies. The corresponding antibody positivities for the controls were 98 (35.4%) for IgG, 77 (27.8%) for IgA, and 64 (23.1%) for both IgG and IgA. When compared, with the control group, the seroprevalence of H. pylori in the Crohn's disease patients was significantly lower (P < or = 0.002). In addition the relative IgG response of the patients was lower than the IgA response. The opposite was true for the controls. There was no difference in the absolute levels of H. pylori antibodies between patients and controls. In the follow-up study two patients initially IgG-positive for H. pylori became negative over time; these patients had been treated for their infection. the rest, who continued to be positive, were not treated. One patient who was initially IgA-positive also became IgA-negative over time. The follow-up group, who were initially IgG- and IgA-negative, remained IgG-negative with time, and two patients became IgA-positive. Findings of anti-H. pylori IgG were confirmed with Western blots. Furthermore, these showed that of the H. pylori-positive patients (indicated by their IgG positivity), 66% were infected with a cytotoxic (cagA-positive) variety, compared to 69.4% of the controls. CONCLUSIONS: Patients with Crohn's disease have a lower prevalence of H. pylori antibodies than an age-matched control group. There is a reversal of the relative IgG and IgA responses in Crohn's disease patients compared with the controls. Of the Crohn's disease patients with H. pylori most are infected with cytotoxic varieties, similar to controls.

Crohn's disease of the upper gastrointestinal tract.

Although Crohn's 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 Crohn's 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 Crohn's disease showed a significant correlation between the activity of the disease, as defined by the Crohn's Disease Activity Index, and the number of plasma cells containing IgM, suggesting a generalized activated humoral defence system during relapse. A diagnosis of Crohn's 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 Crohn's disease. When Crohn's 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 Crohn's 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 Crohn's disease elsewhere in the gastrointestinal tract. Absolute indications for surgical treatment are massive bleeding, progressive stenosis, and extensive fistula formation.

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 Crohn's 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 Crohn's disease. Although corticosteroid-related side-effects are rare, some suppression of the hypothalamic-pituitary-adrenal axis may occur.