Poor diagnostic value of colonic CD44v6 expression and serum concentrations of its soluble form in the differentiation of ulcerative colitis from Crohn's disease

Background—Increased expression ofCD44v6 on colonic crypt epithelial cells in ulcerative colitis has beensuggested as a diagnostic tool to distinguish ulcerative colitis fromcolonic Crohn's disease.
Aims—To investigate colonicCD44v6 expression and serum concentrations of soluble CD44v6 (sCD44v6)in patients with ulcerative colitis and Crohn's disease.
Methods—Colonic biopsy samples wereobtained from 16 patients with ulcerative colitis, 13 with ileocolonicCrohn's disease, and 10 undergoing polypectomy. Serum samples wereobtained from 15 patients with active ulcerative colitis, 20 withactive Crohn's disease, and 20 healthy donors. Colonic CD44v6expression was evaluated immunohistochemically by monoclonal antibody2F10 and the higher affinity monoclonal antibody VFF18. Serum sCD44v6concentrations were measured by ELISA.
Results—2F10 stained colonicepithelium of inflamed ulcerative colitis and Crohn's disease samplesin 80% and 40% of cases, respectively, and VFF18 in 95% and 87%,respectively. Both monoclonal antibodies displayed a sensitivity andspecificity of 60% and 87% to differentiate ulcerative colitis fromcolonic Crohn's disease. Serum concentrations of sCD44v6 were lower inpatients with ulcerative colitis (median 153 ng/ml; interquartile range(IQR) 122-211) compared with Crohn's disease (219; IQR 180-243) andhealthy donors (221; IQR 197-241 (p=0.002)). Its sensitivity andspecificity to discriminate ulcerative colitis from Crohn's diseasewas 75% and 71%, respectively.
Conclusion—Colonic CD44v6 and serumsCD44v6 concentrations do not facilitate reliable differentialdiagnosis between ulcerative colitis and Crohn's disease.

Keywords:CD44 variant 6; differential diagnosis; immunohistochemistry; soluble CD44v6

     

Mast cell mediated ion transport in intestine from patients with and without inflammatory bowel disease

Background—Mast cells have been shown to regulateintestinal ion transport in animal models and normal human colon buttheir physiological role in human intestinal inflammatory disorders is unknown.
Aims—To examine mast cell regulation of iontransport in inflammatory bowel disease (IBD).
Subjects and methods—Small and large intestinewas obtained from patients with and without IBD undergoing surgicalresection. Short circuit current (Isc) responses to rabbitantihuman IgE, histamine, and electrical stimulation were measured inUssing chambers. Specimens were also examined for mast cell numbers and degree of inflammation.
Results—Isc responses to anti-IgEand histamine were smaller in magnitude in IBD compared with non-IBDtissues. In all tissues, anti-IgE Isc responses werereduced by about 80% in chloride free buffer. The histamineH₁ receptor antagonist, pyrilamine, decreased anti-IgEresponses in non-IBD tissues. Greater inhibition with pyrilamine wasseen in IBD small intestine but its effect was less in IBD colon.Histamine pretreatment of non-IBD control tissues reduced anti-IgEresponses to levels seen in IBD colon but had no effect in smallintestine. Mast cell numbers were greater in IBD compared with non-IBDsmall intestine while no differences were observed between the colonicgroups. Isc responses to anti-IgE were not correlated withthe degree of mucosal inflammation.
Conclusions—This study provides further evidencethat mast cells are capable of mediating alterations of ion transportin human gut but that this regulatory role may be altered in IBD. Thedata suggest that prior activation of mast cells with release ofhistamine may account for the reduced secretory response to anti-IgEobserved in IBD colonic tissues.

Keywords:mast cells; intestine; ion transport; histamine; ulcerative colitis; Crohn's disease

     

Anti-Saccharomyces cerevisiae mannan antibodies combined with antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease: prevalence and diagnostic role

^a Service d'Hépato-Gastroentérologie, Hôpital Huriez, ^b Laboratoire de Parasitologie-Mycologie, ^c Service d'Epidémiologie et de Santé Publique, CH et U Lille, ^d Département d'Hématologie-Immunologie-Cytogénétique, CH Valenciennes, France, ^e Division of Gastroenterology and the UCLA Inflammatory Bowel Disease Center, Department of Medicine, UCLA School of Medicine, Los Angeles, California, USA

Correspondence to: Dr J-FColombel, Clinique des Maladies de l'Appareil Digestif et de la Nutrition, Hôpital Huriez, CH et U Lille, 59037 Lille, France.

Accepted for publication 19 January 1998

Background—Perinuclear antineutrophil cytoplasmic autoantibodies (pANCA) are a well recognised marker for ulcerative colitis. Antibodies to oligomannosidic epitopes of the yeast Saccharomyces cerevisiae (ASCA) are a new marker associated with Crohn's disease.
Aims—To assess the value of detecting pANCA and/or ASCA for the diagnosis of ulcerative colitis and Crohn's disease.
Methods—Serum samples were obtained from 100 patients with Crohn's disease, 101 patients with ulcerative colitis, 27 patients with other miscellaneous diarrhoeal illnesses, and 163 healthy controls. Determination of pANCA and ASCA was performed using the standardised indirect immunofluorescence technique and an ELISA, respectively.
Results—The combination of a positive pANCA test and a negative ASCA test yielded a sensitivity, specificity, and positive predictive value of 57%, 97%, and 92.5% respectively for ulcerative colitis. The combination of a positive ASCA test and a negative pANCA test yielded a sensitivity, specificity, and positive predictive value of 49%, 97%, and 96% respectively for Crohn's disease. Among patients with miscellaneous non-inflammatory bowel disorders, three were ASCA positive and two were pANCA positive. One control was ASCA positive. The presence of ASCA in patients with Crohn's disease was associated with small bowel involvement.
Conclusion—ASCA and pANCA are strongly associated with Crohn's disease and ulcerative colitis, respectively. Combination of both tests could help the diagnosis of inflammatory bowel disease.
(GUT 1998;:788-791)

Keywords: Crohn's disease;  ulcerative colitis;  antineutrophil cytoplasmic autoantibodies;  anti-Saccharomyces cerevisiae mannan antibodies

     

Crohn's-like reaction in diverticular disease

Background—Diverticulitis and Crohn's diseaseaffecting the colon occur at similar sites in older individuals, and incombination are said to carry a worse prognosis than either disease inisolation. It is possible that diverticulitis may initiate inflammatorychanges which resemble Crohn's disease histologically, but do notcarry the clinical implications of chronic inflammatory bowel disease.
Aims—To evaluate histological features andclinical outcome in individuals initially diagnosed histologically ashaving both Crohn's colitis and diverticulitis.
Patients—Eleven consecutive individuals having acolonic resection showing histological features of both Crohn'sdisease and diverticulitis.
Methods—Retrospective review of histologicalspecimens, case notes, and discharge letters.
Results—In nine patients, the Crohn's-likereaction was confined to the segment bearing diverticula. They had noclinical evidence of Crohn's disease.
Conclusion—A Crohn's-like inflammatory responsecan be a localised reaction to diverticulitis and does not necessarilyindicate chronic inflammatory bowel disease.

Keywords:Crohn's disease; diverticulitis; colitis; histology

     

Impairment of intestinal glutathione synthesis in patients with inflammatory bowel disease

Background—Reactive oxygen species contribute totissue injury in inflammatory bowel disease (IBD). The tripeptideglutathione (GSH) is the most important intracellular antioxidant.
Aims—To investigate constituent amino acid plasmalevels and the GSH redox status in different compartments in IBD withemphasis on intestinal GSH synthesis in Crohn's disease.
Methods—Precursor amino acid levels were analysedin plasma and intestinal mucosa. Reduced (rGSH) and oxidisedglutathione (GSSG) were determined enzymatically in peripheral bloodmononuclear cells (PBMC), red blood cells (RBC), muscle, and innon-inflamed and inflamed ileum mucosa. Mucosal enzyme activity ofγ-glutamylcysteine synthetase (γGCS) and γ-glutamyl transferase(γGT) was analysed. Blood of healthy subjects and normal mucosa froma bowel segment resected for tumour growth were used as controls.
Results—Abnormally low plasma cysteine and cystinelevels were associated with inflammation in IBD (p<10^-4).Decreased rGSH levels were demonstrated in non-inflamed mucosa (p<0.01) and inflamed mucosa (p=10^-6) in patients withIBD, while GSSG increased with inflammation (p=0.007) compared withcontrols. Enzyme activity of γGCS was reduced in non-inflamed mucosa(p<0.01) and, along with γGT, in inflamed mucosa(p<10^-4). The GSH content was unchanged in PBMC, RBC, and muscle.
Conclusions—Decreased activity of key enzymesinvolved in GSH synthesis accompanied by a decreased availability ofcyst(e)ine for GSH synthesis contribute to mucosal GSH deficiency inIBD. As the impaired mucosal antioxidative capacity may further promote oxidative damage, GSH deficiency might be a target for therapeutic intervention in IBD.

Keywords:Crohn's disease; ulcerative colitis; glutathione; amino acids; γ-glutamylcysteine synthetase; mucosa

     

Imbalance of the interleukin 1 system in colonic mucosa—association with intestinal inflammation and interleukin 1 receptor agonist genotype 2

Background—Interleukin 1 (IL-1) α and β arepotent cytokines which play key roles in inflammation. They arecontrolled by IL-1 receptor antagonist (IL-1ra).
Aims—To investigate the influence of mucosalinflammation and IL-1ra genotype on the IL-1ra:IL-1 balance.
Patients and methods—IL-1α, IL-1β, and IL-1rawere measured by enzyme linked immunosorbent assay (ELISA) in biopsyspecimens taken from inflamed and non-inflamed colon of 60 patientswith Crohn's disease (CD), 34 with ulcerative colitis (UC), 15 inflammatory controls, and 103 non-inflamed controls. IL-1ra genotypewas determined by polymerase chain reaction and gel electrophoresis.
Results—IL-1α and IL-1β were significantlyincreased in inflamed mucosa in inflammatory bowel disease (IBD) (CD:53.5 (22.4) and 409.9 (118.7) pg/mg protein, respectively; UC: 18.9 (6.8) and 214.5 (78.2) pg/mg, respectively) and non-IBD patients (19.2(7.4) and 281.4 (121.0) pg/mg, respectively; p<0.0001) compared withnormal controls (2.8 (0.6) and 30.6 (5.6) pg/mg, respectively). In CDIL-1α and β were also significantly increased in non-inflamed mucosa (6.1 (1.3) pg/mg and 88.7 (17.4) pg/mg, respectively;p<0.0012). IL-1ra:(IL-1α+β) ratios were significantly decreased ininflamed mucosa of patients with CD (182 (45); p<0.0001), UC (425 (136); p=0.0018) and without IBD (221 (76); p<0.0001), and innon-inflamed mucosa in CD (369 (149); p<0.0001) compared with normalcontrols (1307 (245); p<0.0001). Patients with IL-1ra genotype 2 hadslightly but significantly reduced mucosal IL-1ra concentrations(p=0.003). The greatest difference was seen in colonic biopsy specimensfrom patients with inflamed Crohn's disease.
Conclusion—Mucosal inflammation can modulate thebalance of the IL-1:IL-1ra system in colonic mucosa.

Keywords:interleukin 1; interleukin 1 receptor antagonist; inflammatory bowel disease; Crohn's disease; mucosal inflammation; genotype

     

Monozygotic twins with Crohn's disease and ulcerative colitis: a unique case report

Background—A large number of monozygotic anddizygotic twin pairs with inflammatory bowel disease have beenreported. To date no twin pair has developed phenotypically discordantinflammatory bowel disease. This case report is the first documentedoccurrence of discordant inflammatory bowel disease occurring inmonozygotic twins.
Case report—Twenty two year old identical maletwins presented within three months of each other with inflammatorybowel disease that proved to be discordant in overall disease type,disease distribution, clinical course, and histopathological findings. Twin 1 developed a severe pancolitis necessitating total colectomy while twin 2 developed a predominantly distal patchy colitis with frequent granulomas, controlled by aminosalicylates. Twin 1 was antineutrophil cytoplasmic antibody (ANCA) negative at the time oftesting while twin 2 (Crohn's disease) was ANCA positive.Significantly, the twins possessed the HLA type DR3-DR52-DQ2 previouslyassociated with extensive colitis.
Conclusion—This case report confirms the importantrole played by genetic factors in the development of inflammatory bowel disease. It also highlights the crucial role of undeterminedenvironmental agents in dictating disease expression and phenotype.

Keywords:monozygotic twins; ulcerative colitis; Crohn'sdisease; inflammatory bowel disease

     

Appendicectomy, childhood hygiene, Helicobacter pylori status, and risk of inflammatory bowel disease: a case control study

Aims—To examine the relation between inflammatorybowel disease and appendicectomy, childhood domestic hygiene, andHelicobacter pylori infection.
Methods—Case control study involving 213 patientswith ulcerative colitis, 110 with Crohn's disease, and 337 controlshaving elective surgery.
Results—Nine patients with ulcerative colitis(4.5%) reported a previous appendicectomy compared with 57 controls(19%) (odds ratio (OR) 0.20, 95% confidence interval (CI) 0.1-0.4,p<0.0001). The inverse association was unaffected by excludingoperations performed after the age of onset of ulcerative colitis andwas stronger for appendicectomy performed before age 20 (OR 0.14). Noassociation with appendicectomy was found for Crohn's disease and noassociations with tonsillectomy for either disease. The availability ofa fixed hot water supply in early childhood (before age 11) wasassociated with Crohn's disease (OR for hot water not always versusalways available 0.56, 95% CI 0.3-0.9, p=0.02) but not withulcerative colitis. No other aspect of domestic hygiene before or afterage 11 was associated with either Crohn's disease or ulcerativecolitis. Although H pylori seroprevalence was positively associated with overcrowding (p<0.001) and the absence of running hotwater in childhood it was not associated with the presence of eitherCrohn's disease or ulcerative colitis. H pyloriseroprevalence was no lower in patients who had been exposed tosulphasalazine than in controls or those not exposed.
Conclusions—Our findings confirm the stronginverse association between previous appendicectomy and the developmentof ulcerative colitis and suggest that the protective effect is greaterfor appendicectomy performed in childhood.

Keywords:inflammatory bowel disease; appendicectomy; tonsillectomy; childhood hygiene; Helicobacter pylori; sulphasalazine

     

Peripheral arthropathies in inflammatory bowel disease: their articular distribution and natural history

Background—Peripheral arthropathy is a well-recognised complication of inflammatory bowel disease (IBD). Little is known of its natural history, but a variety of joint involvement has been described, from large joint pauciarticular arthropathy to a rheumatoid pattern polyarthropathy.
Aims—To classify the peripheral arthropathies according to pattern of articular involvement, and study their natural history and clinical associations.
Methods—The case notes of all patients attending the Oxford IBD clinic were reviewed, and information on general disease characteristics, extraintestinal features, and arthropathy extracted. This was confirmed by direct patient interview using questionnaires at routine follow up. Patients with recorded joint swelling or effusion were classified as type 1 (pauciarticular) if less than five joints were involved and type 2 (polyarticular) if five or more were involved. Patients without evidence of swelling were classified as arthralgia.
Results—In total, 976 patients with ulcerative colitis (UC) and 483 with Crohn''s disease (CD) were reviewed. Type 1 occurred in 3.6% of patients with UC (83% acute and self-limiting) and in 6.0% of those with CD (79% self-limiting); 83% and 76%, respectively, were associated with relapsing IBD. Type 2 occurred in 2.5% of patients with UC and 4.0% of those with CD; 87% and 89%, respectively, caused persistent symptoms whereas only 29% and 42%, respectively, were associated with relapsing IBD.
Conclusion—Enteropathic peripheral arthropathy without axial involvement can be subdivided into a pauciarticular, large joint arthropathy, and a bilateral symmetrical polyarthropathy, each being distinguished by its articular distribution and natural history.

     

Ulcerative colitis has an aggressive course after orthotopic liver transplantation for primary sclerosing cholangitis

Background—The course of inflammatory boweldisease after liver transplantation has been reported as variable withusually no change or improvement, but there may be an increased risk of early colorectal neoplasms. In many centres steroids are often withdrawn early after transplantation and this may affect inflammatory bowel disease activity.
Aims—To evaluate the course of inflammatory boweldisease in primary sclerosing cholangitis transplant patients who weretreated without long term steroids.
Methods—Between 1989 and 1996, there were 30 patients transplanted for primary sclerosing cholangitis who survivedmore than 12 months. Ulcerative colitis was diagnosed in 18 (60%)patients before transplantation; two had previous colectomy. Allpatients underwent colonoscopy before and after transplantation andwere followed for 38 (12-92) months. All received cyclosporin ortacrolimus with or without azathioprine as maintenance immunosuppression.
Results—Ulcerative colitis course aftertransplantation compared with that up to five years beforetransplantation was the same in eight (50%) and worse in eight (50%)patients. It remained quiescent in eight and worsened in four of the 12 patients with pretransplant quiescent course, whereas it worsened inall four patients with pretransplant active course (p=0.08). New onset ulcerative colitis developed in three (25%) of the 12 patients withoutinflammatory bowel disease before transplantation. No colorectal cancerhas been diagnosed to date.
Conclusions—Preexisting ulcerative colitis oftenhas an aggressive course, while de novo ulcerative colitis may developin patients transplanted for primary sclerosing cholangitis and treated without long term steroids.

     

A simple clinical colitis activity index

Background—The appropriate medicaltreatment of patients with ulcerative colitis is determined largely bythe severity of symptoms. Hospital assessment of the severity ofdisease activity includes investigation of laboratory indices andsigmoidoscopic assessment of mucosal inflammation.
Aims—To develop a simplifiedclinical colitis activity index to aid in the initial evaluation ofexacerbations of colitis.
Methods—The information fordevelopment of the simple index was initially evaluated in 63 assessments of disease activity in patients with ulcerative colitiswhere disease activity was evaluated using the Powell-Tuck Index (whichincludes symptoms, physical signs, and sigmoidoscopic appearance). Thenew index was then further evaluated in 113 assessments in a differentgroup of patients, by comparison with a complex index utilisingclinical and laboratory data, as well as five haematological andbiochemical markers of disease severity.
Results—The newly devised SimpleClinical Colitis Activity Index, consisting of scores for five clinicalcriteria, showed a highly significant correlation with the Powell-TuckIndex (r=0.959, p<0.0001) as well as thecomplex index (r=0.924, p<0.0001) and alllaboratory markers (p=0.0003 to p<0.0001).
Conclusions—This new Simple ColitisActivity Index shows good correlation with existing more complexscoring systems and therefore could be useful in the initial assessmentof patients with ulcerative colitis.

Keywords:ulcerative colitis; disease activity

     

Five genetic markers in the interleukin 1 family in relation to inflammatory bowel disease

Background—An imbalance between theproinflammatory cytokine interleukin 1β (IL-1β) and theanti-inflammatory cytokine IL-1 receptor antagonist (IL-1ra) has beenpostulated as a pathogenic factor in inflammatory bowel disease (IBD).
Aims—To study allelic frequenciesof novel polymorphisms in the genes for IL-1β and IL-1ra in patientswith IBD and to assess the relation between ex vivo cytokine productionand allelic variants of the IL-1β and IL-1ra genes.
Subjects—Two hundred and seventyhealthy controls, 74 patients with ulcerative colitis (UC), 72 withCrohn's disease (CD), 40 with primary sclerosing cholangitis for theallelic frequencies, and 60 healthy individuals for the ex vivostimulation test.
Methods—Genotyping was performed bypolymerase chain reaction and subsequent cleavage with specificendonucleases (Mwo1, MspAI1, Alu1, Taq1, BsoF1) for five novelrestriction fragment length polymorphisms (RFLPs) in the genes forIL-1ra and IL-1β.
Results—No significant differences were found inthe allelic frequencies or allele carriage rates of the markers in theIL-1β and IL-1ra genes between CD, UC, and healthy controls. Noassociation between the genetic markers and cytokine production levelswas observed. Patients with UC carried the combination of both the infrequent allele of the Taq1 RFLP and the Mwo1 RFLP significantly morefrequently (35.2% in UC versus 71.1% in controls).
Conclusions—UC is associatedwith carriage of both infrequent alleles of the Taq1 and Mwo1 RFLPs.However, it could not be confirmed whether the association reflects apathogenic mechanism underlying UC.

     

Expression of cell membrane complement regulatory glycoproteins along the normal and diseased human gastrointestinal tract

Background/Aims—Uncontrolled complementactivation may be of immunopathological importance in inflammatorydiseases of the gastrointestinal tract. Expression of membrane boundfactors that regulate complement activation was therefore studied in situ.
Methods—Frozen tissue specimens were obtained frompatients with Helicobacter pylori gastritis, coeliacdisease, Crohn's disease, or ulcerative colitis, and fromhistologically normal controls. Sections were examined byimmunofluorescence with monoclonal antibodies to protectin (CD59),decay accelerating factor (DAF), and membrane cofactor protein (MCP).
Results—Protectin and MCP were widely expressed innormal and diseased mucosae. MCP was generally observed basolaterallyon all epithelial cells, whereas apical protectin expression was moreintense on the epithelium of normal colonic mucosa than in the normalduodenum (p = 0.001). Epithelial DAF and to some extent protectin wereupregulated in gastritis, coeliac disease, and inflammatory boweldisease. Areas of the stomach with intestinal metaplasia expressed DAF,unlike the adjacent gastric epithelium. Parietal cells of the gastricbody expressed neither protectin nor DAF.
Conclusion—Epithelial complement inhibitorymolecules were expressed differently at various normal gastrointestinalsites and also in association with mucosal disease, suggesting variable protective potential. Such molecules could play a role in the development of gastric atrophy by protecting areas of intestinal metaplasia. Conversely, parietal cells appeared to be potentially vulnerable targets for complement attack.

Keywords:Helicobacter pylori; coeliac disease; Crohn's disease; ulcerative colitis; immunofluorescence; complementregulatory proteins

     

Association of Susceptibility Locus for Inflammatory Bowel Disease on Chromosome 16 with Both Ulcerative Colitis and Crohn's Disease

A susceptibility locus for inflammatory bowel disease (IBD) on chromosome 16 (IBD1) has been linked to Crohn's disease in genome-wide linkage studies. We performed a case–control study with two markers for this locus using leukocyte DNA from 127 Crohn's patients, 83 ulcerative colitis patients, and 74 control patients. Allele, genotype, and haplotype frequencies of the polymerase chain reaction products were determined using autoradiography. Haplotype frequencies differed for ulcerative colitis and Crohn's disease, particularly for haplotype CC (22% ulcerative colitis vs 10% Crohn's disease, P = 0.002 ² = 10.0) and haplotype CD (18% Crohn's disease vs 9% ulcerative colitis, P = 0.025 ² = 5.02). These data demonstrate the association of the IBD1 locus with both ulcerative colitis and Crohn's disease in a group of unrelated IBD patients. The use of such microsatellite markers when combined with others, might help distinguish ulcerative colitis from Crohn's disease in patients with ambiguous clinical and histological features.     

Factors affecting splanchnic haemodynamics in Crohn's disease: a prospective controlled study using Doppler ultrasound

Background—Current knowledge on splanchnichaemodynamics in Crohn's disease is limited.
Aims—To investigate which features of Crohn'sdisease affect splanchnic haemodynamics, and to establish whetherportal vein (PV) and superior mesenteric artery (SMA) blood supplyreflects clinical or biochemical activity of Crohn's disease.
Methods—Seventy nine patients with Crohn'sdisease and 40 controls were evaluated by Doppler ultrasound (US). Themean velocity of PV and SMA flow, the volume of blood flow of the PVand SMA, and the resistance index of SMA were studied. A series ofclinical, biochemical, and US variables including Crohn's diseaseactivity index, serum C reactive protein concentrations, diseaseduration and its anatomical location, smoking habits, abdominalcomplications, and current medical therapy, as well as the maximumbowel wall thickness as measured by US, were determined. The relationbetween PV and SMA blood flow and these variables was assessed byunivariate and multivariate analysis.
Results—Patients with Crohn's disease hadsignificantly higher PV and SMA flow and a lower SMA resistance indexthan controls. Stepwise multiple regression analysis identified bowelwall thickness and location of the disease as the main predictivevariables of both PV and SMA blood flow variation, accounting for 36%and 45% of their variability, respectively. No relation was foundbetween splanchnic haemodynamics and disease activity.
Conclusion—A hyperdynamic mesenteric circulationdoes exist in Crohn's disease; however splanchnic blood flow does notreflect the clinical or biochemical activity of the disease, but seems to be linked more to other Crohn's disease characteristics, such asmaximum bowel thickness and anatomical location.

Keywords:Crohn's disease; Doppler ultrasound; splanchnicblood flow

     

Sclerosing cholangitis, race and sex

Background—Primary sclerosing cholangitis developsin 3-10% of patients with ulcerative colitis, and may be associatedwith an increased cancer risk. Ulcerative colitis is probably less common in people of African origin than in populations of European descent.
Aims and methods—To review the records of allpatients under regular follow up for ulcerative colitis at StBartholomew's Hospital (London, UK) , a tertiary referral centre,prompted by discovering a cluster of cases with common features.
Results and conclusions—Among 166 patients withulcerative colitis under regular follow up, only four (all women) areof African or Caribbean genetic origin, and three of these havedeveloped sclerosing cholangitis within three years of presentationwith colitis, compared with four of 162 patients of European or Asian descent (odds ratio 119, 95% confidence interval 8-3837; p=0.0002). This cluster, which is not explained by common HLA DR or DQ type, suggests that Africans and Afro-Caribbeans, especially women, may be atincreased risk of sclerosing cholangitis. This may reflect geneticinfluences on the development of enteric and hepatobiliary inflammatory disease.

Keywords:sclerosing cholangitis; ulcerative colitis; geneticsof inflammatory bowel disease; racial effects on disease

     

Controlled trial of antituberculous chemotherapy in Crohn's disease: a five year follow up study

Background—It has been suggested thatMycobacterium paratuberculosis is the cause of Crohn'sdisease. In a previous report the immediate effect of two yearstreatment with antituberculous chemotherapy showed no clinical benefit.
Aims—To assess both the immediate and longer termeffect of treatment on the disease.
Methods—Patients were followed for five yearsfrom their date of entry to the study. One hundred and thirty patientsentered the initial study, and of these 111 (81%) were followed regularly.
Results—Overall, there was no evidence ofconsistent benefit or disadvantage from antituberculous chemotherapy inany of the assessments made, including the number of acute relapses,surgical episodes, hospital admissions, disease activity, blood tests, or medication required for Crohn's disease during the follow up period.
Conclusion—The absence of any benefit at the endof the initial two year trial period, and during the three yearsubsequent follow up, fails to support the hypothesis that mycobacteriaplay an important part in the pathogenesis of Crohn's disease, or that antituberculous chemotherapy may be of benefit.

Keywords:Crohn's disease; mycobacteria; antituberculuschemotherapy

     

Incidence of Crohn's disease in Stockholm County 1955-1989

Aim—To evaluate the incidence of Crohn'sdisease in Stockholm County between 1955 and 1989.
Methods—A cohort of 1936 patients withCrohn's disease was retrospectively assembled. Incidence rates andchanges in disease distribution were assessed.
Results—The mean increase inincidence was 15% (95% confidence intervals 12% to 18%) per fiveyear period with a mean annual incidence rate at 4.6/10⁵during the last two decades. The mean incidence for the entire studyperiod was similar for men and women. The mean age at diagnosis increased from 25 years in 1960-64 to 32 years in 1985-89, partly because of an increasing proportion of patients aged at least 60 yearsat diagnosis. The proportion of patients with colonic Crohn's diseaseat the time of diagnosis increased from 15% to 32% (17% difference;95% confidence intervals 12% to 23%) whereas the proportion ofpatients with ileocaecal disease decreased from 58% to 41% (17%difference; 95% confidence intervals 10% to 24%) during the studyperiod. Elderly patients had a higher proportion of small bowel diseaseand a lower proportion of ileocolonic disease compared with the youngerpatients.
Conclusion—The incidence rate ofCrohn's disease in Stockholm has stabilised at 4.6/10⁵ andthe proportion of elderly patients has increased during a 35 yearperiod. Colonic Crohn's disease has increased in frequency with areciprocal decrease in ileocaecal disease.

Keywords:Crohn's disease; inflammatory bowel disease; incidence; epidemiology