Antineutrophil cytoplasmic antibodies in inflammatory bowel disease: diagnostic tool or research procedure?

Antineutrophil cytoplasmic antibodies, initially detected in the sera of patients with Wegener's granulomatosis and other forms of systemic vasculitides, have also been observed in patients with inflammatory bowel disease, with a higher prevalence in ulcerative colitis. In this study, we investigated the prevalence of these antibodies in the sera of 42 patients with ulcerative colitis and 48 patients with Crohn's disease, and the possible correlations with disease activity and extent, extraintestinal complications, and therapy. Antineutrophil cytoplasmic antibodies were found in 30 out of the 42 patients with ulcerative colitis (71.4%); only 16 out of the 48 patients (33.3%) with Crohn's disease were positive (p < 0.001), and the prevalent pattern was perinuclear. No correlations with disease activity and extent, extraintestinal complications, or surgical or medical treatment were found. Our data indicate that in the case of inflammatory bowel disease, the search for antineutrophil cytoplasmic antibodies still remains a research procedure and cannot be used for clinical diagnosis.     

Incidence of inflammatory bowel diseases in the department of Puy-de-D?me in 1993 and 1994. EPIMICI. Epidémiologie des Maladies Inflammatoires Cryptogenetiques de l'Intestin group

The aim of this prospective epidemiological study was to investigate the incidence of Inflammatory Bowel Disease in the Puy-de-D?me county using the same methodology as EPIMAD's registry. METHODS: From 01/01/93 to 31/12/94, each gastroenterologist (n = 22) collected patients consulting for the first time with clinical symptoms compatible with inflammatory bowel disease. Data were reported on a questionnaire by an interviewer practitioner. The final diagnosis of Crohn's disease and ulcerative colitis was made in a blind manner by two expert gastroenterologists and recorded according to the Calkin's criteria as definite, probable, or possible diagnosis, or unclassifiable chronic colitis or acute colitis. RESULTS: 167 new cases were identified: 112 (67.1%) inflammatory bowel disease for the combined group of definite and probable cases with 79 Crohn's disease (70.5%), 29 ulcerative colitis (25.9%) of which 11 ulcerative proctitis (37.9%), 4 unclassifiable chronic colitis (3.6%) and 55 acute colitis (32.9%). The crude and age-adjusted incidence (per 10(5)/year) was respectively 6.6 and 5.7 for Crohn's disease and 2.4 and 1.9 for ulcerative colitis. The highest age-specific incidence rate for Crohn's disease was between 40-49 years (14.1) and for ulcerative colitis between 80-89 years (6.8). The female/male ratio was 0.8 for Crohn's disease and 1.1 for ulcerative colitis. The median age at the time of diagnosis was 42.6 years for Crohn's disease and 35.3 years for ulcerative colitis. CONCLUSIONS: These preliminary findings revealed a high incidence of Crohn's disease and low of ulcerative colitis in this county. However, these results must be managed carefully because these data were recorded only on two years and the inflammatory bowel disease classified possible and acute colitis require a follow-up.     

Pericarditis in chronic inflammatory bowel disease: underlying disease or side effects of therapy? Clinical problem solving

Pericarditis and myocarditis are rare extraintestinal manifestations of chronic inflammatory bowel disease (ulcerative colitis and Crohn's disease). Pericarditis as a side effect induced by sulfasalazine or 5-aminosalicylic acid, drugs used in the therapy of these diseases, was first described only 7 years ago. In older case reports the relationship between the use of these drugs and pericarditis is unclear. We analyze the reported cases of 68 patients (38 men, 24 women) with ulcerative colitis (n = 45) or Crohn's disease (n = 15) who had one or more episodes of pericarditis or myopericarditis. Pericarditis was not associated with high activity of bowel disease in all cases. In most cases therapy with corticosteroids led to uneventful recovery. In drug induced pericarditis omission of the 5-ASA therapy was sufficient in a few cases. There was one fatal case (with myocarditis). The decision whether pericarditis is a symptom of the underlying disease or a side effect of the drug used for the treatment of the disease is not always easy. We present an analysis (clinical problem solving) of a pertinent observation in a patient with Crohn's disease and pericarditis, showing the dilemma of pericarditis in chronic inflammatory bowel disease and its therapy.     

Epitope mapping of cytochrome P450cam (CYP101)

OBJECTIVE: A retrospective study of women with inflammatory bowel disease, aged 16-45 years during the 20-year period 1967-1986, was carried out in North East Scotland. METHOD: Five-hundred and three women were identified: 15 patients had died from unrelated causes and 22 had emigrated, but 409 of the remaining 466 patients (88%) replied to the study questionnaire. RESULTS: Women with ulcerative colitis and Crohn's disease had normal fertility when compared with the general population of north east Scotland. However, unresolved infertility problems were more frequent in women who had undergone surgery for inflammatory bowel disease compared with those who had not (12% vs. 5% for Crohn's disease; 25% vs. 7% for ulcerative colitis). Disease relapse rates did not increase in pregnancy. CONCLUSIONS: Overall, at conception women with active disease were as likely to have a normal full-term pregnancy as those in remission. However, spontaneous abortion occurred in five (36%) pregnancies of women who had undergone previous surgery for Crohn's disease and had evidence of recurrent disease. Three of these pregnancies were associated with active disease.     

Epiphysis-metaphysis bone ischemia in hemorrhagic rectocolitis and Crohn's disease

Aseptic osteonecrosis is a rare extraintestinal manifestation in patients with inflammatory bowel disease; its true prevalence is not precisely known. Steroid treatment undoubtedly participates in the pathophysiology of avascular osteonecrosis, however, other factors like hypercoagulability may be involved. Two cases of bilateral osteonecrosis of the knees--the first occurring during the course of ulcerative colitis, the second in a patient presenting with Crohn's disease--are described. Specific location of the lesions and regression of symptoms, as well as the importance of magnetic resonance imaging for early recognition of osteonecrosis, are noteworthy.     

Hepatobiliary complications of idiopathic intestinal inflammations

Extraintestinal manifestations and metabolic complications are very frequent in patients with idiopathic inflammations of the gut and are encountered in at least 35% of these patients. In Crohn's disease extraintestinal manifestations are more frequent than in ulcerative colitis, in particular when the large bowel is affected. Metabolic complications are the result of inflammatory changes of the small intestine or develop as a result of the reduced reabsorption surface of the gut. As to the relationship to the activity of the idiopathic inflammation of the gut, extraintestinal manifestations can be differentiated into those which depend on the activity of the basic disease and those which lack this dependence. From the aspect of a long-term prognosis extraintestinal manifestation independent on the activity of the inflammation of the gut are much more serious, because as a rule they have a long-term and usually progressive trend. The most serious extraintestinal complication is primary sclerotizing cholangitis which in the majority of patients leads to destruction of the biliary pathways and the development of biliary cirrhosis. Depending on the predominantly affected site of the biliary system, primary sclerotizing cholangitis is divided into three types. It is encountered much more frequently in ulcerative colitis than in Crohn's disease. Treatment of primary sclerotizing cholangitis is not very effective. At present it appears that the only drug with an effect on the course of the disease is long-term administration of urodesoxycholic acid. For patients with manifestations of hepatic insufficiency the only solution is transplantation of the liver. In all patients where the diagnosis of primary sclerotizing cholangitis was established, at the same time the possibility of inclusion in a transplantation programme should be considered. The relationship between sclerotizing cholangitis and pericholangitis has not been resolved conclusively. At present the majority of authors is inclined to believe that pericholangitis is part of changes associated with sclerotizing cholangitis. Other hepatobiliary complications of idiopathic inflammations of the gut such as cholelithiasis and parenchymatous liver damage, steatosis of the liver and chronic autoimmune hepatitis are not such a serious problem as sclerotizing cholangitis.     

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.     

Sweet's syndrome: an unusual cutaneous feature of Crohn's disease or ulcerative colitis. The South West Gastroenterology Group

Sweet's syndrome is characterized by tender, red inflammatory nodules or papules, usually affecting the upper limbs, face or neck. It is part of the group of acute neutrophilic dermatoses that includes pyoderma gangrenosum, but can be distinguished by its appearance, distribution and histological features. Four patients with Sweet's syndrome and Crohn's disease are reported. A total of 30 cases from the literature suggest that Sweet's syndrome is an unusual extraintestinal manifestation of either Crohn's disease or ulcerative colitis. There is a strong predilection for women (87%), patients with colonic disease (100%) and those with other extraintestinal features (77%). The rash is associated with active disease in 67-80%, but may precede the onset of intestinal symptoms in 21% and has been reported 3 months after proctocolectomy for ulcerative colitis.     

The majority of myeloid-antigen-positive (My+) childhood B-cell precursor acute lymphoblastic leukaemias express TEL-AML1 fusion transcripts

BACKGROUND & AIMS: Crohn's disease and ulcerative colitis show a familial aggregation. In both diseases, anti-goblet cell autoantibodies (GABs) have been described. The aim of this study was to define the role of GABs in the pathogenesis of inflammatory bowel disease. METHODS: The study population comprised 61 patients with ulcerative colitis, 76 patients with Crohn's disease, 101 first-degree relatives of patients with ulcerative colitis, and 105 first-degree relatives of patients with Crohn's disease. Thirty-five patients with infectious enterocolitis and 56 healthy unrelated subjects served as controls. Autoantibodies were detected by indirect immunofluorescence. RESULTS: Thirty-nine percent of patients with ulcerative colitis (24 of 61) and 30% of patients with Crohn's disease (23 of 76) were positive for GABs. GABs were detected in 21% (21 of 101) of first-degree relatives of patients with ulcerative colitis and in 19% (20 of 105) of first-degree relatives of patients with Crohn's disease. In patients with infectious enterocolitis and in healthy controls, GABs were seen in 3% (1 of 35) and 2% (1 of 56), respectively. The differences between control groups and both groups of patients or their first-degree relatives were significant. CONCLUSIONS: The high prevalence in first-degree relatives suggests that GABs may represent a marker characterizing susceptibility to inflammatory bowel disease.     

The surgical management of nonspecific inflammatory bowel disease: a small personal experience

AIMS: To document the surgical management of patients with non specific inflammatory bowel disease managed in the colorectal service, University Department of Surgery, Wellington School of Medicine. METHODS: Retrospective analysis of patients managed between April 1975 and March 1990. RESULTS: Sixty five patients had inflammatory bowel disease. Twenty one (11 males) had ulcerative colitis and 44 (18 males) had Crohn's disease. There were no Maori. One hundred and twenty three operations were performed overall. Ten patients with ulcerative colitis were operated upon as emergencies. Five presented with fulminating disease. Six patients successfully underwent restorative proctocolectomy although one was subsequently thought to have had Crohn's disease. Overall there was one postoperative death. Crohn's disease patients underwent a total of 91 operations. Twenty nine operations were elective and 15 emergency during the first surgical admission. The commonest indication for surgery was stricture. The commonest operation performed was right hemicolectomy. Chest, wound and central line sepsis were the commonest postoperative problems. There were two postoperative deaths. Six patients favoured a series of relatively minor perineal operations to proctectomy. CONCLUSION: A cautious staged approach to the surgical management of inflammatory bowel disease patients resulted in only three deaths-an overall mortality rate of 4.6%. Accordingly we advocate a policy of expectant surgery to relieve symptoms or correct complications in patients with Crohn's disease. We believe that patients requiring surgery for ulcerative colitis should be offered the choice of either restorative proctocolectomy or panproctocolectomy and ileostomy.     

Measurement of rectal blood flow by laser Doppler flowmetry in inflammatory bowel disease

BACKGROUND/AIMS: Vascular alterations have been suggested as pathogenic factors in inflammatory bowel disease, particularly Crohn's disease. The aim of our study was to assess rectal blood flow in patients with active inflammatory bowel disease involving the rectum. METHODOLOGY: Endoscopic measurement of rectal blood flow was performed by laser Doppler flowmetry in 45 subjects divided into three groups: healthy controls, ulcerative colitis and rectal Crohn's disease. RESULTS: Rectal perfusion was found to be significantly impaired in patients with ulcerative colitis, but not in those with Crohn's colitis. CONCLUSIONS: Our results confirm the role of local ischemia in ulcerative colitis, but do not support the theory that vascular factors play a key role in the pathogenesis of Crohn's disease.     

Incidence of inflammatory bowel disease in northern France (1988-1990)

There were no data concerning the incidence of inflammatory bowel disease (IBD) in France. The aim of this study was to investigate the incidence of Crohn's disease and ulcerative colitis in northern France. This prospective population based study was realised through the gastroenterologists of the region Nord-Pas de Calais and the Somme Department. Each gastroenterologist referred patients consulting for the first time with clinical symptoms compatible with IBD. Data were collected by an interviewer practitioner present at the gastroenterologist's consulting room. Two independent expert gastroenterologists assessed each case in a blind manner and made a final diagnosis of Crohn's disease, ulcerative colitis, ulcerative proctitis, or unclassifiable chronic colitis. From 1988 to 1990, 1291 cases of IBD were recorded: 674 (52%) Crohn's disease, 466 (36%) ulcerative colitis including 162 proctitis (35%), and 151 (12%) unclassifiable chronic colitis. The mean annual incidence was 4.9 per 100,000 for Crohn's disease and 3.2 for ulcerative colitis. The sex ratio F/M was 1.3 for Crohn's disease and 0.8 for ulcerative colitis. The highest age specific incidence rate for Crohn's disease was between 20 and 29 years: 13.1 for women and 9.8 for men. The highest age specific incidence rate for ulcerative colitis was between 20 and 39 years: 5.5 for women and 6.5 for men. This first French prospective study has shown an incidence rate for Crohn's disease comparable with that seen in north European studies but lower than that seen for ulcerative colitis. These results could be related to the different environmental factors or the genetic background of the population studied, or both.     

Anti-neutrophil cytoplasmic antibodies in inflammatory bowel disease with special attention for IgA-class antibodies

Perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) of the IgG class have been reported in inflammatory bowel disease, mainly in ulcerative colitis. Since this disease affects the gastrointestinal tract, we determined whether IgA class ANCA were present in inflammatory bowel disease. We used an indirect immunofluorescence assay for IgG and IgA ANCA testing. Sera from 34 patients with Crohn's disease and 29 patients with ulcerative colitis were collected together with clinical and laboratory data. We found IgA class ANCA of a perinuclear type in 52% of patients with ulcerative colitis and in 9% of Crohn's disease patients. There was a significant association between the presence of IgA ANCA and the occurrence of blood in the feces in the ulcerative colitis group (P = 0.03). IgG ANCA was found in 56% of patients with ulcerative colitis and in 7% of patients with Crohn's disease. Because of partial overlap between IgG and IgA ANCA positivity, the sensitivity of ANCA testing in ulcerative colitis increased from 56% up to 78% by combining IgG and IgA assays. In conclusion, IgA ANCA occurs with a high prevalence in ulcerative colitis. Moreover there is a possible relationship between IgA ANCA and disease activity in ulcerative colitis.     

Antineutrophil cytoplasmic antibodies in Estonian patients with inflammatory bowel disease. Prevalence and diagnostic role

BACKGROUND/AIMS: In Estonia, the incidence of ulcerative colitis and especially Crohn's disease appears to be rare. Antineutrophil cytoplasmic antibodies (ANCA) are frequently found in ulcerative colitis but less frequently in Crohn's disease, their pathophysiological significance is still unclear. METHODOLOGY: Fifty-nine serum samples from patients with ulcerative colitis, 17 with Crohn's disease, 25 with irritable bowel syndrome, and 86 healthy persons were studied. Sera were analyzed for the presence of ANCA by indirect immunofluorescence, and enzyme-linked immunosorbent assay for specific ANCA using different antigens was performed. RESULTS: ANCA were detected in 29 of 59 (49%) patients with ulcerative colitis, 4 of 17 (24%) patients with Crohn's disease, and in 4 of 111 (4%) controls. The immunofluorescence staining was mostly perinuclear (pANCA). There was no correlation between ANCA and the duration or extent of the inflammatory bowel disease. In specific enzyme-linked immunosorbent assays, only 14 sera elicited binding above the normal range. CONCLUSIONS: Although the prevalence of ulcerative colitis and Crohn's disease in Estonia is much lower than in European countries, there seem to be no differences in the presence of ANCA.     

Inflammatory bowel disease

Although ulcerative colitis and Crohn's disease are relatively uncommon disorders, most primary care practices include a number of individuals with these diagnoses. Much of the initial evaluation and long-term care of these patients is managed or coordinated by their primary care physicians. A familiarity with current principles of diagnosis and treatment is essential. Ulcerative colitis and Crohn's disease are related, immunologically mediated disorders of unknown cause. Both are characterized by chronic relapsing courses, frequent need for surgical intervention, and increased colorectal cancer risk. Significant differences are seen between these two inflammatory bowel disease syndromes, in their histopathologic features, clinical manifestations, and response to treatment. This review focuses on the colorectal manifestations of inflammatory bowel disease, emphasizing clinical presentation, approach to diagnosis, medical and surgical management, and long-term prognosis.     

Familial empirical risks for inflammatory bowel disease: differences between Jews and non-Jews

The Jewish population has an increased frequency of inflammatory bowel disease compared with their non-Jewish neighbours. Genetic factors have been implicated in the aetiology of this disorder and may contribute to ethnic differences. This study determined the familial empirical risks for inflammatory bowel disease in the first degree relatives of inflammatory bowel disease probands (for both Jews and non-Jews) for the purpose of accurate genetic counselling and genetic analysis. A total of 527 inflammatory bowel disease patients from Southern California (291 Jews and 236 non-Jews) were questioned about inflammatory bowel disease in their first degree relatives (a total of 2493 individuals). Since inflammatory bowel disease has a variable and late age of onset, age specific incidence data were used to estimate the life time risks and to make valid comparisons between the different groups. In the first degree relatives of non-Jewish probands, the life time risks for inflammatory bowel disease were 5.2% and 1.6% when probands had Crohn's disease and ulcerative colitis respectively. These values were consistently lower than the corresponding risks for relatives of Jewish patients -7.8% and 4.5% for Crohn's disease and ulcerative colitis probands respectively (p value for comparison between Jews and non-Jews: 0.028; between ulcerative colitis and Crohn's disease: 0.005). These data provide the requisite basis for genetic counselling for these disorders in the white American population. In addition, these different empirical risks for relatives of Jewish and non-Jewish probands allow rejection of single Mendelian gene models for inflammatory bowel disease, but are consistent with several alternative genetic models.     

Association between inflammatory bowel disease and sarcoidosis. Report of two cases and review of the literature

BACKGROUND: Common etiopathogenic factors may explain the association of systemic sarcoidosis with inflammatory bowel disease. METHODS: We report two cases of such an association: one of sarcoidosis that developed 2 years after proctocolectomy for ulcerative colitis and one of sarcoidosis and Crohn's colitis. Factors like increased cellular immunity or circulating immunocomplexes or autoantibodies may have a role. Exogenous agents or familiarity may also be involved. CONCLUSIONS: It is postulated that the association between sarcoidosis and inflammatory bowel disease (both ulcerative colitis and Crohn's disease) does not occur by chance alone and that the two conditions may share some genetic or immunologic alterations. The two diseases, however, follow an independent clinical course.     

Correlation of a common mutation in the methylenetetrahydrofolate reductase gene with plasma homocysteine in patients with premature coronary artery disease

BACKGROUND: Recent clinical trials have demonstrated that methotrexate may have an important therapeutic role in the treatment of patients with inflammatory bowel disease, who are either refractory or intolerant to traditional medical therapy. The aim of this study was to evaluate the pharmacokinetics of low-dose oral methotrexate in patients with inflammatory bowel disease. METHODS: Methotrexate (12.5 mg) was given orally to nine patients with inflammatory bowel disease: five with Crohn's disease, and four with ulcerative colitis, and to six patients with rheumatoid arthritis who served as a control group. Blood samples were drawn at specific intervals to evaluate methotrexate plasma levels. RESULTS: Methotrexate was rapidly absorbed in all patients. Peak concentrations (Cmax) varied considerably, ranging from 0.25-0.87 micro M. The mean Cmax values were similar in all patient groups (0.59 +/- 0.12, 0.69 +/- 0.16 and 0.54 +/- 0.18 micro M, P not significant) for Crohn's disease, ulcerative colitis and rheumatoid arthritis, respectively. The mean area under curve in 120 min (AUC0-120) was also similar in all patient groups (32.9 + 11.3, 43.6 + 9.9 and 41.8 + 14.9 ng.min/mL, P not significant) for Crohn's disease, ulcerative colitis and rheumatoid arthritis, respectively. The mean time to reach Cmax, (tmax), varied between patient groups (84, 112 and 95 min, respectively, with a significant difference, P < 0.02, between the Crohn's disease and ulcerative colitis groups. A negative correlation was found between methotrexate dosage/kg and Cmax (r = -0.74) only in Crohn's disease patients but not in the other patient groups. CONCLUSIONS: Orally administered methotrexate is well absorbed in patients with inflammatory bowel disease including those with severe small bowel disease or resection. If methotrexate is proven to be effective in inflammatory bowel disease, it should be administered orally.     

Treatment of refractory rapid cycling bipolar disorder with risperidone

BACKGROUND: There is evidence for a hypercoagulable state in inflammatory bowel disease (IBD), and small vessel thrombosis has been identified in the bowel of patients with Crohn's disease, suggesting thrombosis as a possible etiologic factor. Activated protein C (APC) resistance is the most common inherited disorder leading to thrombosis and accounts for 30% to 40% of episodes of idiopathic venous thrombosis. METHODS: The prevalence of APC resistance was studied in 23 patients with IBD (17 with Crohn's disease, 6 with ulcerative colitis) and in 11 control subjects with recurrent abdominal pain or celiac disease, using an APC resistance screening method. RESULTS: One patient with Crohn's disease had a positive screen result, two patients (one with Crohn's, one with ulcerative colitis) had borderline results, and results in all of the control subjects were normal. One patient with Crohn's disease had a history of a thromboembolic event but had a normal screen result. CONCLUSIONS: Activated protein C resistance does not seem to play a major role in the etiology of the hypercoagulable state in inflammatory bowel disease.     

The extra-intestinal complications of Crohn's disease and ulcerative colitis: a study of 700 patients

The records of a series of 700 patients with inflammatory bowel disease, 498 with Crohn's disease and 202 with ulcerative colitis, have been analyzed to determine the relative incidence and characteristic features of their extra-intestinal manifestations. The group with Crohn's disease included 62 with colitis, 223 with ileocolitis, and 213 with regional enteritis. A consideration of the clinical patterns and an understanding of their pathophysiology suggested a subdivision into two main groups: one "colitis related" and one related to the pathophysiology of the small nonspecific third group. Group A, colitis related, comprises joint, skin, mouth, and eye disease. The complications might be immunologically determined, were closely associated with active inflammation, and often responded to medical or surgical treatment of the underlying bowel disease. They occurred in 36% of the entire series of patients: joints were involved in 23%, skin in 15%, and mouth and eye each in 4%. Pyoderma gangrenosum was observed most often in ulcerative colitis and erythema nodosum most often in granulomatous colitis. The incidence of Group A complications was higher in disease involving the colon (42%) than in disease restricted exclusively to the small bowel (23%). There were interrelationships among the various members of Group A, with multiple manifestations occurring in a third of affected patients. Group B, related to small bowel pathophysiology, includes malabsorption, gallstones, kidney stones, and non-calculous hydronephrosis and hydroureter. Disorders in this group were generally related to the severity of the disease in the small bowel and tended to persist even in the absence of active inflammation. In contrast to Group A, this group occurred most frequently in small bowel disease, and least in colonic disease. Malabsorption was virtually confined to the patients with small bowel disease (10% incidence), while gallstones and renal stones were also both more frequent in Crohn's disease (11% and 9% respectively), the latter usually in association with small bowel resection or ileostomy. Group C, found in a small percentage of patients, consists of nonspecific complications, including osteoporosis (3%), liver disease (5%), peptic ulcer (10%), and amyloidosis (1%).