A Case of Sequential Development of Celiac Disease and Ulcerative Colitis

William Dickey

Disclosures

Nat Clin Pract Gastroenterol Hepatol. 2007;4(8):463-467. 

In This Article

Discussion of Diagnosis

Celiac disease is an autoimmune enteropathy primarily affecting the proximal small bowel and triggered in genetically susceptible individuals by exposure to wheat, barley and rye gluten. Over 90% of patients with celiac disease express the major histocompatibility complex human leukocyte antigen (HLA) DQ2 haplotype and most of the rest express HLA-DQ8.[1] The findings of screening studies indicate that celiac disease affects around 0.5-1.0% of members of populations with European ancestry, which includes members of the US population.[2] Gluten enteropathy comprises a spectrum of histologic abnormalities that affect the duodenum and jejunum; the enteropathy was first described by Marsh (later modified by Oberhuber and co-workers).[3] Marsh I enteropathy is defined by an excess of intraepithelial lymphocytes (>30 per 100 enterocytes), Marsh II enteropathy has, in addition, the presence of crypt hyperplasia, and Marsh III enteropathy is the 'classic' celiac lesion, which comprises Marsh I and Marsh II enteropathy plus villous atrophy. Most patients with celiac disease test positive for serum EmA and TTGA, which enables initial tests for celiac disease to be performed by physicians other than gastroenterologists; however, false-negative results occur in 10% of patients or more[4] and duodenal biopsy samples should be obtained for assessment if a diagnosis of celiac disease is suspected.

Clinical Presentation of Celiac Disease

The traditional perception of celiac disease is one of childhood onset and presentation with symptoms directly attributable to malabsorption, which include steatorrhea and weight loss. Nonetheless, despite ingesting gluten since infancy most patients are diagnosed in adulthood; in one Italian study 4% of patients were diagnosed when they were over 65 years of age.[5] For many cases in the past, diagnosis in adulthood reflected a failure on the part of clinicians to consider a diagnosis of celiac disease, resulting in delayed diagnosis despite the presence of symptoms for many years.[5,6] Only a minority of cases have the typical clinical presentation owing to malabsorption. Patients are frequently overweight at presentation[6,7] and in one unit, fewer than a third of patients reported diarrhea as a symptom at presentation.[4] Patients can present with nonspecific gastrointestinal symptoms including dyspepsia and reflux, or with non-gut symptoms including anemia, chronic fatigue, peripheral neuropathy and ataxia.

The histologic changes that accompany the development of gluten enteropathy might develop for the first time in later life. Around 10% of patients who test positive for serum EmA have no, or only mild (Marsh I) enteropathy, which if left untreated will proceed to villous atrophy in most cases.[8] Sanders et al. describe the case of a 79-year-old male who, despite having symptoms of celiac disease, had negative serological test results and histology. In spite of these negative results, the disease progressed to strongly positive serology and total villous atrophy within 3 months.[9]

The case patient's initial symptoms of flatulence and weight loss prompted investigation for celiac disease by serological testing and duodenal biopsy; the findings from both investigations were initially negative, and positive results were obtained only after the onset of iron-deficiency anemia. Negative investigations for celiac disease do not preclude its diagnosis later in life. HLA-DQ typing, which was unavailable at the facility handling this case, can determine which patients are HLA-DQ2 and HLA-DQ8 negative and are, therefore, unlikely to develop celiac disease in the future.[1] Research has shown that a 'trigger'--often unidentified--is required to precipitate the onset of clinical celiac disease--pregnancy and the puerperium are the best documented examples.[10]

Failure to Respond to a Gluten-Free Diet

Patients with celiac disease can fail to respond to the initial introduction of a gluten-free diet or have a recurrence of symptoms after initial improvement, despite maintaining gluten exclusion. The most feared causes of either scenario are complicating malignancy, notably enteropathy-associated T-cell lymphoma, or refractory sprue, which is defined as the failure of a gluten-free diet to restore normal small-bowel architecture and function. Both of these complications are associated with considerable morbidity and mortality.[11] Assuming that the initial diagnosis of celiac disease is correct, continued deliberate or inadvertent gluten ingestion should be stopped. Other causes of persistent symptoms with increased prevalence in celiac disease include lactose intolerance, exocrine pancreatic insufficiency, bacterial overgrowth and microscopic (lymphocytic or collagenous) colitis.[12,13]

Initially, the case patient's celiac disease responded well to gluten exclusion, as shown by the resolution of her symptoms, the recovery of her hemoglobin level and the disappearance of EmA and TTGA from her serum; in addition, subsequent follow-up confirmed the absence of histologic abnormalities in duodenal biopsy samples. Enteroscopy and CT scanning did not detect evidence of lymphoma on diagnosis of celiac disease. Subsequent wireless capsule endoscopy, which is a valuable imaging technique for the diagnosis of small-bowel tumors, also did not detect evidence of lymphoma.[14] There was no evidence of collagenous or lymphocytic colitis in the patient's colon histology, and her response to active treatment of ulcerative colitis and maintenance of gluten exclusion avoided the need to carry out investigations for pancreatic insufficiency, lactose intolerance and bacterial overgrowth.

Colon Pathology in Patients With Celiac Disease

The association between celiac disease and microscopic colitis (either collagenous or lymphocytic) is well recognized. In addition, Yang et al.[15] reported that the prevalence of ulcerative colitis and Crohn's disease was significantly higher among patients with celiac disease than in the general population (prevalence rate ratios of 3.6 and 8.5, respectively). In 5 out of 10 patients with both celiac disease and IBD the diagnosis of celiac disease preceded that of IBD (by 7 months to 12 years); in addition, the symptoms of 4 of these 5 patients were improved by a gluten-free diet, which suggests that gluten is not the trigger for IBD in patients with celiac disease. Similarly, the case patient had excellent clinical, serological and histologic improvement of celiac disease before the onset of her ulcerative colitis symptoms. Finally, while there is no firm evidence to support an association between celiac disease and colonic neoplasia, both conditions are common and can coexist by chance in older patients.[16] Colonoscopy should, therefore, be part of the initial work-up in patients who are 40 years of age or older who present with iron-deficiency anemia or diarrhea, even if initial tests indicate celiac disease.

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