Celiac disease (gluten-sensitive enteropathy).

Celiac disease may be initially detected in either children or adults, even in the elderly. This small intestinal mucosal disorder is gluten-dependent and causes nutrient malabsorption, often with diarrhea and weight loss. Diagnosis depends on detection of typical biopsy changes in the proximal small bowel along with an unequivocal response to a gluten-free diet. Recurrent changes usually result from poor adherence to the gluten-free diet, sometimes intentional, or from consumption of unsuspected gluten sources. In others, the original diagnosis may not be correct (e.g., duodenal involvement with Crohn's disease) or another cause for symptoms may have supervened (e.g., collagenous colitis, functional bowel disease). Rarely, a complication may occur (e.g., collagenous sprue, lymphoma). In some, the gluten-dependent nature of the small bowel disorder was not initially documented and biopsy changes continued despite a gluten-free diet. These have a sprue-like intestinal disorder, also labeled unclassified sprue. This represents a small, but likely, heterogeneous group, and in these, intractable symptoms may be present and, in some, lymphoma is eventually diagnosed.

Relevance of segmental colitis with diverticulosis (SCAD) to other forms of inflammatory bowel disease.

A well localized inflammatory process involving only the sigmoid colonic segment associated with diverticulosis (SCAD), has become increasingly recognized as a distinct clinical and pathological disorder, usually described in older adults, often with rectal bleeding. Although some resolve spontaneously, most patients appear to respond to treatment only with 5-aminosalicylate. Endoscopic evaluation reveals a nonspecific inflammatory process localized in the sigmoid colon that usually completely resolves with histologically normal colonic mucosa. Recurrent symptoms with evidence of recurrent segmental colitis may occur, but most have an entirely benign clinical course. Further definition of the underlying molecular signalling that occurs in this apparently distinctive disorder may be critically important to understand the elements of a colonic inflammatory process that can completely and spontaneously resolve.

Pearls and pitfalls in the diagnosis of adult celiac disease.

In adults with diarrhea or suspected malabsorption, a diagnosis of celiac disease requires that two criteria be fulfilled: first, a demonstration of typical pathological changes of untreated disease in biopsies from the proximal small bowel; and second, evidence should exist that clinical (and/or pathological) changes are gluten-dependent, most often as an unequivocal response to a gluten-free diet. Pathological abnormalities of celiac disease may include severe ('flat') or variably severe (mild or moderate) small bowel mucosal architectural abnormalities that are associated with both epithelial cell and lymphoid cell changes, including intraepithelial lymphocytosis. Architectural changes tend to be most severe in the duodenum and proximal jejunum and less severe, or absent, in the ileum. These findings, while characteristic of celiac disease, are not specific because several other conditions can produce similar changes. Some serological assays (eg, tissue transglutaminase antibody assays) are very useful screening tools in clinical practice because of their high specificity and sensitivity, but these do not provide a definitive diagnosis. The most critical step in the diagnosis of celiac disease is the demonstration of its gluten-dependent nature. The clinical response to gluten restriction in celiac disease is usually reflected in the resolution of diarrhea and weight gain. Normalization of biopsy changes can be first shown in the most distal intestinal sites of involvement, and later, sometimes only after prolonged periods (months to years) in the duodenum. Rarely, recurrent (or refractory) celiac disease may occur after an initial gluten-free diet response. Finally, some with 'sprue-like intestinal disease' cannot be classified because a diet response fails to occur. This may be a heterogeneous group, although some are eventually found to have a malignant lymphoma.

Clinical and histological predictors of response to medical therapy in collagenous colitis.

OBJECTIVES: Collagenous colitis (CC) is an uncommon form of inflammatory bowel disease. The response to typical medical therapies (antimotility agents, 5-aminosalicylic acid [5-ASA], and corticosteroids) is variable. We aimed to determine if there are clinical or histological variables that can predict response to medical therapy. METHODS: All cases of CC were identified in three tertiary care medical centers. All charts of included patients were reviewed and clinical variables (age, gender, duration of symptoms, frequency of bowel movements, and the use of nonsteroidal anti-inflammatory drugs [NSAIDs]) were recorded. Available histology slides were reviewed by one GI pathologist. Intraepithelial inflammation, epithelial loss or detachment, inflammation in the lamina propria, presence of eosinophilia, crypt inflammation, Paneth's cell metaplasia, and collagen layer thickness were recorded. Depending on their response to therapy, patients were divided into three groups: 1) spontaneous recovery or response to antidiarrheal agents alone, 2) response to 5-ASA agents, and 3) response to corticosteroids after failure of antidiarrheal agents and 5-ASA. RESULTS: Ninety-four patients with CC were identified. Of these, 62 patients were included. The median age was 58 (range = 20-85), and 88% were female. Among the histological parameters only the degree of inflammation in the lamina propria significantly differed between the three response groups (p = 0.007). Patients who required corticosteroids had greater inflammation. Among the clinical parameters age at presentation and use of NSAIDs significantly differed between groups. In the antidiarrheal group, patients tended to be more elderly, and in the corticosteroid group, more patients were on NSAIDs. CONCLUSIONS: 1) The degree of lamina propria inflammation can be used as a histological predictor to guide treatment in patients with CC. 2) Patients who responded to antidiarrheal agents or had spontaneous remissions were significantly older than those patients requiring 5-ASA compounds or corticosteroids. 3) Patients who were taking NSAIDs were more likely to require corticosteroid therapy, presumably reflecting more severe disease.

Familial occurrence of lymphocytic colitis.

The familial occurrence of lymphocytic colitis in a female parent and her two female children is reported. No other genetically based disorder, including celiac disease, was evident. For both children, the age of diagnosis was more than two decades younger than the age of recognition of disease in the parent, and some clinical features, including the requirement for pharmacological agents in both children, suggested that their disease severity was more significant than that of the involved parent. These characteristics of a familial disease have been previously reported and labelled 'genetic anticipation' in some monogenetic forms of neurological disease, as well as in other types of inflammatory bowel diseases, including Crohn's disease. Alternatively, a common cohort effect related to a pathological environmental factor may have played a role in the pathogenesis of this disorder.

Anticipation in an Indo-Canadian family with Crohn's disease.

Genetic anticipation, associated elsewhere with monogenic neurological disorders, has been hypothesized to be present in familial forms of Crohn's disease. Usually, with studies of parent-child pairs, the parent who is initially diagnosed is older at the onset of disease than the child. With each successive generation, an apparent increase in disease severity or behaviour occurs. This phenomenon is believed to have a molecular basis. In the present report, an Indo-Canadian family with Crohn's disease is described. In all members of the family, disease was diagnosed only after prolonged residence in Canada, supporting the view that Crohn's disease arises in individuals with a genetic predisposition following exposure to some, as yet unknown, common environmental factor. Three siblings with Crohn's disease, first diagnosed between ages 15 and 27 years, or six to 11 years after arrival in Canada, had phenotypically concordant disease localized in the ileum and colon, with fistulizing complications, including perianal sepsis. Crohn's disease was only diagnosed in the father at the age of 76 years, almost three decades after his arrival in Canada. His disease was localized to the ileum and had a fibrostenosing behaviour. This is the first reported instance of familial Crohn's disease in an immigrant population, illustrating potential biases in genetically based studies of Crohn's disease that rely solely on phenotypic expression.

Topographic mapping of collagenous gastritis.

A 74-year-old woman was investigated for abdominal pain and diarrhea. Endoscopic examinations including biopsies of the stomach and colon demonstrated the typical subepithelial deposits characteristic of collagenous gastritis and collagenous colitis. Histochemical and ultrastructural methods confirmed the presence of collagen in the subepithelial deposits. The topographic distribution of these collagen deposits and their relationship to the inflammatory process in the stomach were then defined by endoscopic mapping and multiple site biopsies of the mucosa in the gastric body and antrum. These studies indicate that collagenous gastritis not only is distinctive, but also is a far more extensive and diffuse inflammatory process than has previously been appreciated.

Colorectal cancer complicating Crohn's disease.

Some earlier studies have indicated that patients with inflammatory bowel disease, especially those with long-standing and extensive ulcerative colitis, have an increased risk of colorectal cancer. Moreover, others in tertiary care centres have suggested that patients with Crohn's disease also have a higher risk of colorectal cancer. Canadian data on colorectal cancer in Crohn's disease appear to be limited. For this investigation, a single clinician database of 877 patients with Crohn's disease was used. Altogether, there were six patients with colorectal cancer (ie, overall rate of 0.7%). All of these patients were men with an initial diagnosis of Crohn's disease established at a mean age of approximately 28 years, with either ileocolonic disease or colonic disease alone, but not with ileal disease alone. Although there was a predominance of women in the overall study population (ie, 56.1%), no women developed colorectal cancer. The clinical behaviour of Crohn's disease was classified as nonstricturing in all six patients with colorectal cancer, but in two patients, Crohn's disease was complicated by a perirectal abscess or a fistula. All cancers were located in the rectum and were diagnosed 30 years, 22 years, seven years, 18 years, 20 years and 40 years after Crohn's disease was initially diagnosed. In three patients, the cancer was detected in a residual rectal stump after a partial colon resection at least 10 years earlier. In five patients, localized extension of disease through the serosa, nodal or distant metastases (ie, liver, lung) was found at the time of cancer diagnosis; two patients have since died. The present study confirms that Crohn's disease involving the colon may be a possible risk factor for the development of colorectal cancer, at least in younger men, but, in this study, not in women. However, part of this increased risk in men may have been related to the presence of a rectal stump, rather than to Crohn's disease per se.

Spontaneous peritonitis from perforation of the colon in collagenous colitis.

A 37-year-old woman presented with an acute abdomen following the onset of watery diarrhea. Spontaneous peritonitis was detected, along with evidence of a focal sigmoid colon perforation. Subsequent postoperative colonoscopic studies revealed collagenous colitis with a focal, deep, nongranulomatous ulcer in the sigmoid colon. Although the literature suggests that collagenous colitis tends to have a relatively 'benign' clinical course characterized by chronic or episodic watery diarrhea. Potentially serious and life- threatening complications may occur in this microscopic form of inflammatory bowel disease.

High prevalence of celiac disease in patients with type 1 diabetes detected by antibodies to endomysium and tissue transglutaminase.

OBJECTIVE: To establish the prevalence of celiac disease (CD) in children with type 1 diabetes in British Columbia. PATIENTS AND METHODS: Two hundred thirty-three children with type 1 diabetes were prospectively screened for CD using blind testing with the current 'gold standard', immunoglobulin A endomysium antibody (EmA), and the novel immunoglobulin A tissue transglutaminase (tTG) antibody. Those children with positive results were offered small bowel biopsy; a gluten-free diet was recommended if CD was confirmed. RESULTS: Nineteen children were positive for EmA and had an elevated tTG level. One patient from this group was already known to have CD, and the other 18 patients consented to biopsy. One biopsy was normal, three biopsies demonstrated elevated intraepithelial lymphocyte counts with normal morphology and 14 biopsies had morphological changes consistent with CD. Growth parameters were normal in all patients, and nine of 19 children who were positive for EmA were asymptomatic. Seven patients had mild elevation of tTG levels alone. Two children from this latter group had normal biopsies, and five declined biopsy. CONCLUSIONS: At least 14 new cases of CD were detected in addition to four known cases, yielding an overall biopsy-confirmed prevalence of CD of 7.7% (18 of 233). The present study confirms that CD is as prevalent in the pediatric type 1 diabetic population in British Columbia as it is in Europe. Serological screening of these children is important because many children have no symptoms or signs suggestive of CD. This study suggests that tTG serology may also be useful in monitoring response and compliance with a gluten-free diet.

Meckel's diverticulum in Crohn's disease.

Meckel's diverticulum is a congenital abnormality of the distal ileum associated with failed vitelline duct closure. Detailed pathological studies have estimated its frequency to be about 2% of the general population, and it has been anecdotally recorded in patients with Crohn's disease. Most patients with Crohn's disease have imaging studies of the small intestine during the course of their disease, and often, an intestinal resection. Thus, it seems possible to estimate the prevalence of Meckel's diverticula in Crohn's disease. In addition, patient characteristics may be important, especially if management of Crohn's disease is altered. Of 877 patients with Crohn's disease, 10 (about 1%) had a Meckel's diverticulum diagnosed, including six men and four women. All were diagnosed with Crohn's disease before age 50 years and seven were diagnosed before age 30 years. There were five with ileocolonic disease, two with colon-only disease and three with ileum-only disease. The clinical behaviour of five patients could be classified as penetrating and two as stricturing. A total of 311 patients had an ileocolonic resection, including eight (about 2%) with a Meckel's diverticulum. In contrast to some case reports, no heterotopic mucosa was detected and the Meckel's diverticulum was incidental and, apparently, an unexpected finding. In each case, the diverticulum was not involved with Crohn's disease but was included in the ileal resection. These results suggest that the overall prevalence of a Meckel's diverticulum is not increased in Crohn's disease but may result in resection of additional small intestine.

Application of the Vienna Classification for Crohn's disease to a single clinician database of 877 patients.

An international working party at the World Congress of Gastroenterology held in Vienna, Austria from September 6 to 11, 1998 defined a classification for Crohn's disease based on patient age at diagnosis (eg, less than 40 years of age, 40 years of age or older), disease location (eg, terminal ileum, colon, ileocolon or upper gastrointestinal tract) and behaviour (eg, stricturing, penetrating). Disease location in the upper gastrointestinal tract was defined by disease being present proximal to the terminal ileum, regardless of terminal ileal or colon involvement. A 20-year, single clinician database of 877 patients from a university campus hospital was used, and comprised 492 women (56.1%) and 385 men (43.9%). Of these patients, 740 (84.4%) were diagnosed before age 40 years and 137 (15.6%) were diagnosed by 40 years of age or older. Disease was located in the terminal ileum alone in 222 patients (25.3%), colon alone in 238 patients (27.2%) and ileocolon in 304 patients (34.6%). Another 113 patients (13.1%) had disease in the upper gastrointestinal tract, usually with disease also in the terminal ileum (23 patients), colon (12 patients) or ileocolon (71 patients). Only seven of 877 patients had disease located in the upper gastrointestinal tract alone with no distal disease. Disease behaviour could be classified as nonstricturing and nonpenetrating in 256 patients (29.2%), stricturing in 294 patients (33.6%) and penetrating in 327 patients (37.2%). Of the 877 patients with Crohn's disease, 837 were white, 38 were Asian and two were black. In this tertiary care setting of a single clinician practice in a Canadian teaching hospital at the University of British Columbia, Crohn's disease predominantly affects women, and young adults with a high rate of stricturing and penetrating complications.

Pouchitis-associated iritis (uveitis) following total proctocolectomy and ileal pouch-to-anal anastomosis in ulcerative colitis.

A 26-year-old woman with ulcerative colitis treated with a proctocolectomy and ileal pouch-to-anal anastomosis developed an erosive and ulcerative pouchitis. Although no ophthalmological manifestations were present before the staged surgical procedures, iritis developed after appearance of the pouchitis. Both conditions subsequently resolved with oral corticosteroids and metronidazole.

Increased prevalence of celiac disease in girls with Turner syndrome detected using antibodies to endomysium and tissue transglutaminase.

OBJECTIVE: To establish the prevalence of celiac disease (CD) in girls with Turner syndrome (TS) in British Columbia. METHODS: Forty-five girls with TS were prospectively screened for CD using blinded testing with the current 'gold standard' - immunoglobulin A (IgA) endomysium antibody (EmA) and the novel IgA tissue transglutaminase antibody (tTG). Those with positive results were offered small bowel biopsies, and a gluten-free diet was recommended if CD was confirmed. RESULTS: One asymptomatic prepubertal East Indian girl was positive for EmA, had an elevated tTG concentration of 560 U/mL and histological evidence of CD. Seven girls were negative for EmA but had elevated tTG concentrations (175 to 250 U/mL); five were white, one was Asian and one was East Indian. Small bowel biopsies were performed on three girls, and the histologies were normal. The remaining four patients declined biopsy. CONCLUSIONS: One girl with TS was identified with CD from 45 screened, giving an overall biopsy-confirmed prevalence of 2.2%. This study confirms previous observations placing girls with TS at higher risk for CD and suggests a similar high prevalence in British Columbia.

Prevalence of celiac disease in collagenous and lymphocytic colitis.

Both collagenous and lymphocytic colitis have been described in patients with celiac disease, suggesting an association between the conditions. Over the past few years, the availability, sensitivity and specificity of serological markers for celiac disease have improved - the most recent advancement being the description of tissue transglutaminase as the major antigen for endomysium antibody. A quantitative ELISA was used to measure titres of immunoglobulin A (IgA) antibody to tissue transglutaminase (tTG) along with an immunofluorescent technique for IgA endomysium antibody (EmA) in 15 patients with lymphocytic colitis and eight with collagenous colitis to determine whether celiac disease latency could be detected. One patient with lymphocytic colitis demonstrated both elevated titres of tTG antibody and positive EmA, and small bowel biopsy confirmed celiac disease. One patient with collagenous colitis had a slightly elevated titre of tTG antibody with a negative EmA, and results of a small bowel biopsy were normal. Three other patients with lymphocytic colitis were already treated for previously diagnosed celiac disease. The prevalence of celiac disease occurring in lymphocytic colitis was found to be 27%, but no cases of celiac disease in association with collagenous colitis were found.

Granulomatous osteonecrosis in Crohn's disease.

A 25-year-old white woman was diagnosed with Crohn's disease involving the small and large intestines. She had a complex clinical course that required treatment with multiple pharmacological agents, including intravenous, oral and rectal corticosteroids. She also received parenteral nutrition with lipid emulsions. Finally, repeated intestinal resections and drainage of perianal abscesses were required. Her disease was complicated by gallstones, urolithiasis and hip pain. After osteonecrosis was diagnosed, joint replacements were performed. Review of the pathological sections from the resected hip, however, resulted in detection of granulomatous inflammation with multinucleated giant cells - the histological 'footprint' of Crohn's disease in the gastrointestinal tract. Because prior specialized perfusion fixation pathological studies of the intestine in Crohn's disease have shown that granulomas are located in the walls of blood vessels, a possible mechanism for the pathogenesis of osteonecrosis in Crohn's disease is chronic microvascular ischemia of bone.

Small intestinal mucosal biopsy for investigation of diarrhea and malabsorption in adults.

The use of small intestinal biopsy for diagnosis in diarrhea and suspected malabsorption depends on an optimal interaction between the clinician-endoscopist and the pathologist. This necessitates open and interactive communication between involved physicians and an appreciation for correct tissue handling and biopsy orientation in the endoscopy unit and the pathology laboratory. Classification of biopsy changes on the basis of architectural abnormalities in the small intestinal biopsy may be helpful in defining the diagnosis and include severe (flat) or variably severe (mild or moderate) abnormalities. For some small intestinal disorders that are characterized by diarrhea or malabsorption, the biopsy findings may be distinctive and lead to a specific diagnosis. For others, like celiac disease, the changes are less specific, and it has become better recognized that an increasing number of conditions can produce similar histopathologic changes. Definition of typical gluten-sensitive biopsy changes in this disorder is critical.

T cell lymphoma of the thyroid gland in celiac disease.

Previous studies have reported the association between celiac disease and T cell lymphoma of the intestine as well as hepatosplenic lymphoma, a specialized peripheral type of T cell lymphoma. In this report, a 66-year-old woman with dermatitis herpetiformis and biopsy-defined celiac disease developed a thyroid mass that proved to be a T cell lymphoma. A T cell lymphoma in the setting of celiac disease appears to be unique. The thyroid gland, due to its shared embryological developmental links with the gastrointestinal tract, is possibly another site of extranodal lymphoma linked to celiac disease.