Faculty Bibliography

A 67-yr-old woman with a 25-yr history of Crohn's disease, maintained on near-continuous corticosteroids (prednisone 10 mg daily) over a 6-yr period, underwent ileocolic resection for obstruction. Pathology revealed Crohn's disease, multiple nodules of Kaposi's sarcoma, and cytomegalic inclusion bodies with confirmation of cytomegalovirus by shell vial immunofluorescence. Testing for HIV serum antibody has been repeatedly negative. Crohn's disease, Kaposi's sarcoma, and cytomegalovirus have been clinically in remission for 5 yr

OBJECTIVE: Recent studies have suggested that a susceptibility gene located on chromosome 16 and designated IBD1 may contribute to the development of Crohn's disease (CD). However, these findings were observed in predominantly non-Jewish populations; in the three studies where Ashkenazi Jews were included for analysis, the results have been widely divergent. Because Ashkenazi Jews are known to have a higher incidence of the disease than non-Jews, we sought to determine whether this previously reported linkage could be extended to the Ashkenazi population. In addition, we examined whether Ashkenazi Jewish patients with an early age of onset (< or = 21 yr) showed greater evidence of linkage to this locus. METHODS: Linkage analysis for the IBD1 region was performed on 123 Ashkenazi Jewish CD patients distributed among 53 families. Only patients with four Jewish grandparents were considered to be Jewish. Of the 123 Ashkenazi Jewish patients, 75 (61%) had an age of onset < or = 21 yr. RESULTS: Ashkenazi Jews showed only modest evidence of linkage (nonparametric linkage 1.63, p = 0.05) to the IBD1 locus. However, when the Ashkenazi population was subdivided on the basis of age of onset, there was a striking increase in linkage in families where affected individuals had an age of onset < or = 21 yr (nonparametric linkage 3.02, p = 0.002). In contrast, there was no evidence of linkage in the Jewish families where all affected individuals had an age of onset > 21 yr. CONCLUSIONS: The IBD1 gene plays a greater role in conferring susceptibility to CD in Jews with early onset disease than in Jews with late onset disease

Previous studies have suggested that susceptibility to Crohn's disease (CD) is associated with the histocompatibility complex (HLA) class II alleles DR1, DQ5, and DR13 in the Caucasian population, DR7 in the French and German populations, and DR4 and DQ4 in the Japanese population. However, little is known about the relationship between HLA class II alleles and CD in the Jewish population since these previous studies included few Jewish individuals. In order to determine whether the HLA associations observed with predominantly non-Jewish populations were also present in the Jewish CD population and whether there were any HLA class II alleles uniquely associated with CD in the Jewish population, 132 CD patients, of which 82 were Ashkenazi Jewish, were HLA-typed using serologic and DNA methods. Ethnically matched controls were similarly typed. No association with DR1 or DR13 was observed in the Jewish CD population although an association with DR13 (OR [odds ratio] = 5.3, p = 0.02) was observed in the non-Jewish CD population. However, an association with DR15 (OR = 2.7, p = 0.03), which is normally associated with ulcerative colitis, was observed in the Jewish, but not non-Jewish, CD group. In addition, a strong negative association was observed with DR3, which was especially striking in the Jewish population (OR = 0.35, p = 0.025); similar negative associations with DR3 have been observed by others using non-Jewish populations. Furthermore, a significant negative association with DR7 (OR = 0.45, p = 0.04) was observed in the Jewish, but not non-Jewish, population. Consistent with this was the negative association with DQ2 (OR = 0.38, p = 0.005), which is in strong linkage disequilibrium with both DR3 and DR7, in the Jewish, but not non-Jewish, population. These studies support previous suggestions that susceptibility to CD in Jewish and non-Jewish populations is determined by distinct genes and provide further support to the hypothesis that a gene on the DR3 haplotype may protect against CD. Furthermore, protection is conferred by the same or another gene found on Jewish, but not non-Jewish, DR7 haplotypes

We report a 74-yr-old woman with Crohn's disease and acute pancreatitis who, 3 yr after resolution of the latter, developed cystadenocarcinoma of the pancreas. No drug, toxin, or other etiologies including contiguous duodenal involvement were identified as responsible for the pancreatitis, suggesting that pancreatitis was an extraintestinal manifestation of her Crohn's disease. Could Crohn's-associated pancreatitis be a premalignant state for cystadenocarcinoma of the pancreas?

BACKGROUND & AIMS: Recombinant human interleukin 11 (rhIL-11) is a cytokine with thrombocytopoietic activity and anti-inflammatory and mucosal protective effects. The objectives of this study were to investigate the safety and tolerability of rhIL-11 in patients with Crohn's disease and to explore the effects of dose and schedule on platelet count and Crohn's disease activity. METHODS: A multicenter, double-masked, placebo-controlled, dose-escalation study of 76 patients with active Crohn's disease was performed. Patients were randomized to receive subcutaneous placebo or rhIL-11 at doses of 5, 16, or 40 microgram. kg-1. wk-1 given 2 or 5 times weekly for 3 weeks. Clinical and laboratory safety data were recorded, and disease activity was measured at each visit. RESULTS: Subcutaneous injection of rhIL-11 generally was well tolerated. Significantly greater increases in platelet counts were found among patients receiving rhIL-11 40 microgram. kg-1. wk-1 as 2 or 5 weekly doses and 16 microgram. kg-1. week-1 as 5 weekly doses compared with patients receiving placebo (P < 0.05). Patients receiving 16 microgram. kg-1. wk-1 had the highest clinical response rates, with a response seen in 42% of patients (5/12) receiving 5 weekly doses and 33% of patients (4/12) receiving 2 weekly doses, compared with 7% of patients (1/15) receiving placebo. CONCLUSIONS: Short-term treatment with rhIL-11 is well tolerated in patients with active Crohn's disease. The thrombocytopoietic effect of rhIL-11 seems to be both dose and schedule dependent and may be minimized with retained clinical benefit in Crohn's disease at 16 microgram. kg-1. wk-1 given in 2 equal doses.

Recent advances in the therapy of inflammatory bowel disease specifically directed against the inflammatory and immune mechanisms include an impressive and often overwhelming cornucopia of anti-inflammatory agents, immunomodulators, antibiotics, biologicals, topical therapies, nicotine, heparin, and nutritional supplements. The interface of one drug regimen into another may lead to confounding and often confusing programs of treatment. This review will attempt to offer a perspective of care and an update of specific remedies, but the aim is practicality and usefulness, not encyclopedic detail

OBJECTIVE: We sought to examine whether anticipation (an earlier age of onset in succeeding generations) is observed in Crohn's disease (CD) patients within the New York metropolitan area, and whether there are differences in the degree of anticipation with respect to gender and ethnicity of the affected parent. METHODS: Sixty-one parent-child pairs both affected by CD were identified; about half of the pairs were of Ashkenazi Jewish descent. An additional 17 pairs of second-degree relatives with CD were also identified. The intergenerational difference in age at diagnosis (AAD) was used to perform regression analysis and the degree of anticipation among subsets of patients separated on the basis of gender and ethnicity of the transmitting parent was determined. RESULTS: The AAD was consistently (90% of the time) lower in the younger member of the 61 parent-child pairs (35.3+/-1.6 yr vs 20.8+/-1.1 yr, p = 0.0001). Furthermore, the degree of anticipation was significantly greater for father-child pairs (20.6+/-3.2 yr) than for mother-child pairs (11.7+/-2.1 yr). However, when the patient population where the parent had an AAD of < 28 was analyzed separately, there was a lack of clear-cut evidence of anticipation in the population as a whole. Only when the population was subdivided by ethnicity was there convincing evidence of anticipation in the Jewish population. CONCLUSION: Ascertainment bias may be responsible for the apparent anticipation observed in the CD population as a whole or in the nonJewish CD subgroup. However, the Jewish CD population displays strong evidence of anticipation even after correction for ascertainment bias

We report a rare case of a 69-yr-old white man with jejunal diverticulitis with localized perforation and intramesenteric abscess formation. This entity is often overlooked as a cause of acute abdominal pain in the elderly. Although the clinical diagnosis is difficult, a high index of suspicion should warrant a computed tomography scan or enteroclysis