Prior Diagnosis Of Celiac Disease Research Articles

Hippocampal sclerosis is associated with celiac disease type immunity in patients with drug-resistant temporal lobe epilepsy.

A prior small-scale single center study suggested an association between celiac disease (CD)-type immunity and refractory temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS). The present study addresses this putative association in a large, well-characterized group of drug-resistant epilepsy (DRE) patients. These patients were grouped based on the spectrum of CD and gluten sensitivity-associated antibodies. In this cross-sectional study, 253 consecutive adult epilepsy patients (135 females, 118 males; age 16-76years) were categorized into three groups: (i) CD-positive group with either prior diagnosis of CD or CD-specific TG2/EmA antibodies, (ii) AGA-positive group with antigliadin antibodies (AGA) but without CD, and (iii) CD/AGA-negative group without any gluten sensitivity-associated antibodies or CD. Clinical and immunological findings were then compared among the groups. TLE with HS was more common in the CD-positive group compared to CD/AGA-negative group (31.8% versus 11.9%, P = 0.019). Autoimmune disorders were more common in the AGA-positive group than in the CD/AGA-negative group (P = 0.025). Considering HS lateralization; left lateralization was more common in CD-positive group compared to CD/AGA-negative group (71.4% versus 25%, P = 0.030). TG6 seropositivity did not differ among the groups (P > 0.05). This study provides further evidence linking TLE with HS and CD-type autoimmunity suggesting that CD-type immune response to gluten can be one potential mechanism as a disease modifier leading to DRE and HS. Understanding these immunological factors is imperative for developing immunomodulatory or dietary treatments for DRE potentially preventing HS progression.

P12 A flare of dermatitis herpetiformis precipitated by etanercept

Abstract We report the case of a 79-year-old man who presented with an acute, intensely pruritic, widespread rash, which, on examination, consisted of symmetrical, haemorrhagic nodules and vesicles with some desquamation affecting the extensor surfaces of the arms, flexor surfaces of the legs and the natal cleft. He had a history of coeliac disease (for which he had adhered to a strict gluten-free diet since 1997) and rheumatoid arthritis. He had his first dose of the anti-tumour necrosis factor (TNF) agent etanercept prior to this episode to manage his arthritis. A punch biopsy for histopathology showed subepidermal blisters with a predominance of neutrophils. Eosinophils were also present to the level of the eccrine coils within the dermis, with eosinophilic flame figures but no eosinophil spongiosis at the edges of the blister. Direct immunofluorescence showed granular IgM and IgA in the dermal papillae, and a similar reaction was seen with fibrinogen. These histological findings were strongly suggestive of dermatitis herpetiformis (DH). Owing to diagnostic uncertainty on presentation, initial treatment was with high-dose topical steroids and emollient. and a yellow card was completed. Since this presentation, he has had no further flares and has not required dapsone. Multidisciplinary team discussion decided that the patient should avoid other anti-TNF treatments, but he has found relief for multiple months with rituximab and has had no cutaneous adverse events on this agent. The aetiology of DH following anti-TNF treatment is not immediately clear. Increased immunogenicity and cytokine release have been hypothesized to be part of the pathology of many adverse reactions to anti-TNF agents. It is conceivable that the cytokine release ordinarily seen in DH is replicated by the administration of anti-TNF agents. There have been many cases of anti-TNF agents leading to worsening eczema and psoriasis. Interestingly, these conditions have been found to upregulate TNF-α, a feature that is also seen in DH. This appears to be the first case described in the literature of etanercept-induced DH. A reaction with infliximab was reported in 2008, with a similar rash and histology consistent with DH, but it differed as the patient had no prior diagnosis of coeliac disease and presented after their second dose (Marakli SS, Uzun S, Ozbek S, Tuncer I. Dermatitis herpetiformis in a patient receiving infliximab for ankylosing spondylitis. Eur J Dermatol 2008; 18:88–9).

Biochemical abnormalities among patients referred for celiac disease antibody blood testing in a primary health care setting

To investigate possible biochemical abnormalities associated with celiac disease (CD) antibody positivity in a primary health care setting and thereby identify predictors that could potentially reduce diagnostic delay and underdiagnosis of CD. This observational cohort study included measurements of CD antibodies in the Copenhagen Primary Care Laboratory (CopLab) database from 2000 to 2015; CD antibody positivity was defined as tissue transglutaminase antibody IgA or IgG ≥ 7 kU/L and/or deamidated gliadin peptide antibody IgG ≥ 10 kU/L. Individuals with a prior diagnosis of CD were excluded. We examined differences between individuals with positive and negative CD antibody tests regarding the results of biochemical tests performed six months before and one month after the date of the CD antibody test. We identified 76,265 measurements of CD antibodies during 2000–2015, and 57,061 individuals met the inclusion criteria (706 antibody-positive and 56,355 antibody-negative). We found lower ferritin, hemoglobin, cobalamin and folic acid levels and higher levels of transferrin, ALAT (alanine transaminase), and alkaline phosphate among individuals with a positive CD antibody test. Furthermore, we illustrated more measurements below the sex-specific reference intervals for hemoglobin, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), ferritin, cobalamin and folic acid among individuals with a positive CD antibody test. This study identified several biochemical abnormalities associated with CD antibody positivity among individuals referred to CD antibody testing. The pattern of abnormalities suggested that micronutrient deficiencies were prevalent among CD antibody-positive individuals, confirming malabsorption as a sign of CD. These findings illustrate the possibility of reducing diagnostic delay and underdiagnosis of CD.

Natural history and clinical detection of undiagnosed coeliac disease in a North American community.

Coeliac disease is a substantially underdiagnosed disorder, with clinical testing currently guided by case finding. To determine the presence of indications for diagnostic testing and frequency of clinical testing in undiagnosed coeliac disease. This was a case-control study of adults without prior diagnosis of coeliac disease. Undiagnosed cases were identified through sequential serology, and unaffected age- and gender-matched controls were selected. Medical records were systematically reviewed for indications for and evidence of clinical testing. Of 47557 adults, 408 cases of undiagnosed coeliac disease were identified. 408 serology negative matched controls were selected. Eight-matched pairs were excluded, leading to 800 included individuals (61% female; median age 44.2years). The odds of any indication for clinical testing were similar among undiagnosed coeliac disease and controls (odds ratio (OR) 1.18; 95% CI: 0.85-1.63, P=0.32). Most individual indications were not associated with serologic status. Exceptions to this include hypothyroidism, which was more likely in cases of undiagnosed coeliac disease, and dyspepsia and chronic diarrhoea, which were less likely. Cases of undiagnosed coeliac disease were more likely to develop osteoporosis (P=0.005), dermatitis herpetiformis (P=0.006), chronic fatigue (P=0.033), thyroiditis (P=0.003), autoimmune diseases (P=0.008), and have a family member diagnosed with coeliac disease (P=0.001). This study strongly suggests that current case finding is not effective in detecting undiagnosed coeliac disease. Individuals with undiagnosed coeliac disease were more likely than controls to develop indications for testing overtime. A more effective method for detection of coeliac disease is needed.

Machine Learning Using Indications to Test Fails to Identify Undiagnosed Celiac Disease

Introduction: Current guidelines for detecting celiac disease (CD) recommend case-finding, which is targeted testing of individuals considered to be at risk for CD due to associated conditions, signs, and symptoms. Increasing evidence suggests that case-finding is not effective. CD remains largely undiagnosed, and while the benefit of identifying asymptomatic cases is uncertain, detection of symptomatic cases improves morbidity and mortality. We aimed to use machine learning, a form of artificial intelligence where programs learn through exposure to new data, to build a model to identify undiagnosed CD using currently accepted indications to test. Methods: Blood samples collected from 47,557 individuals (age 18-87.7 years) with no prior diagnosis of CD were tested for tissue transglutaminase antibodies, and if positive or equivocal (defined as ≥3.0 U/ML), the samples were subsequently tested for endomysial antibodies. If these were positive, the individual was identified as having undiagnosed CD. 408 cases and 408 age- and gendermatched controls were selected, and 8 matched pairs were removed due to insufficient data, resulting in 400 cases and 400 controls. Medical records were systematically reviewed by a blinded physician for indications to clinically test (Table 1). A variety of indications to test were used to predict the presence of undiagnosed CD. Nine different classifiers including linear, non-linear, tree-based, and ensemble models were trained over a large parameter space. Performance was assessed via ten-fold cross-validation.Table: Table. Indications for Clinical TestingResults: Only two of the models, random forest and bagged classification trees, outperformed random chance at the 5% level. Both had areas under the receiver-operator curve of 0.55, indicating poor discriminatory performance (Figure 1).Figure: Area under the receiver-operator curve (AUC) from out-of-sample crossvalidation. Only the bagged tree (treebag) and random forest (rf) models outperform random chance.Conclusion: This study used machine learning techniques to attempt to develop a model that would identify undiagnosed cases of CD using currently accepted indications to test. Only two models with very low predictive power outperformed random chance in detecting undiagnosed CD. The failure to develop an effective model may be due to the fact that our currently used indications to test do not reflect the symptoms of undiagnosed cases of CD, or that these symptoms may not be severe enough to come to the attention of care providers. This suggests that case-finding based on symptoms may not be effective and that either new indications to test or alternatives to case-finding should be explored.

Duodenal biopsies for the diagnosis of coeliac disease: are we adhering to current guidance?

BackgroundThe British Society of Gastroenterology guidelines recommend taking at least four duodenal biopsy specimens at the time of upper gastrointestinal (UGI) endoscopy if coeliac disease (CD) is suspected and it...

Real-Life Case Finding of Undiagnosed Celiac Disease: Exposing the Celiac Ugly Truth?

Introduction: Celiac disease (CD) is a common but underdiagnosed disorder. Case-finding (testing at-risk groups) is the preferred strategy for clinical detection. The primary aim was to estimate the frequency of indications for clinical testing in adults with undiagnosed CD and seronegative matched referents. The secondary aim was to estimate the frequency of actual clinical testing. Methods: Stored blood samples from 35,299 adults (age 18.1-87.7 years) with no prior diagnosis of CD were tested for tissue transglutaminase antibodies (tTGA). Samples with a positive/equivocal tTGA, defined as ≥3.0 U/ML, were tested for endomysial antibodies (EMA). Undiagnosed CD was defined by a positive EMA. 408 cases with undiagnosed CD were identified. From the tTGA negative individuals, 408 age and gender matched referents were selected. Medical records were systematically reviewed by a medical professional blinded to serology status, for indications for clinical testing, and evidence of clinical testing with serology and/or biopsies. Indications for clinical testing were consistent with the 2013 American College of Gastroenterology guidelines. Conditional logistic regression was used to test the association of case status and indications for clinical testing. Results: Eight matched pairs were excluded due to lack of data. 800 individuals were included (400 with undiagnosed CD and 400 referents), 61% female, median age of 44.2 years. The frequency of any indication for clinical testing was 159 (40%) among undiagnosed CD and 147 (37%) among referents (P=0.32). There was no difference in frequency of most indications for clinical testing among those with and without undiagnosed CD (Table 1). Hypothyroidism, dyspepsia, and chronic diarrhea were exceptions, with the former found more frequently among undiagnosed CD, and the latter two among referents. Frequency of clinical testing was low (2.3% among undiagnosed CD and 6.5% among referents; P=0.005).Table 1: Unadjusted Conditional Logistic Regression of Undiagnosed Celiac Disease and Indications for Clinical TestingConclusion: This is the largest study on real life case-finding in North America. Our study strongly suggests that the current paradigm for clinical detection of CD may not be effective, as most of the generally accepted indications for clinical testing failed to discriminate among persons with undiagnosed CD and matched referents. The study also confirms the low frequency of clinical testing for CD in the community. Clinical testing for CD, particularly with biopsies, was higher in referents, perhaps due to their higher rates of dyspepsia and chronic diarrhea.

Evidence Against Routine Testing of Patients With Functional Gastrointestinal Disorders for Celiac Disease: A Population-based Study

Celiac disease has been linked to irritable bowel syndrome (IBS)-like symptoms in outpatient clinics. Guidelines recommend that all patients with IBS-like symptoms undergo serologic testing for celiac disease, but there is controversy over whether celiac disease is more prevalent in populations with IBS-like symptoms. We aimed to determine whether positive results from serologic tests for celiac disease are associated with IBS and other functional gastrointestinal disorders (FGIDs) in a large U.S. white population. Validated, self-report bowel disease questionnaires (BDQs) were sent to randomly selected cohorts of Olmsted County, Minnesota residents. In separate protocols, serum samples were collected from more than 47,000 Olmsted County residents without a prior diagnosis of celiac disease; we performed serologic tests for celiac disease on stored serum samples from residents who completed the BDQ. Logistic regression was used to test for the association between serologic markers of celiac disease (positive vs negative) and individual FGIDs. A total of 3202 subjects completed the BDQ and had serum available for testing. IBS was identified in 13.6% of these subjects (95% confidence interval [CI], 12.4%-14.8%), and any gastrointestinal symptom occurred in 55.2% (95% CI, 53.5%-56.9%). The prevalence of celiac disease on the basis of serologic markers was 1.0% (95% CI, 0.7%-1.4%). IBS was less prevalent in patients with celiac disease (3%) than patients without celiac disease (14%), although the difference was not statistically significant (odds ratio, 0.2; 95% CI, 0.03-1.5). Abdominal pain, constipation, weight loss, and dyspepsia were the most frequent symptom groups in subjects who were seropositive for celiac disease, but none of the gastrointestinal symptoms or disorders were significantly associated with celiac disease serology. Symptoms indicative of FGIDs and seropositive celiac disease are relatively common in a U.S. white community. Testing for celiac disease in patients with IBS in the community may not have a significantly increased yield over population-based screening in the United States.

Celiac disease evolving into dermatitis herpetiformis in patients adhering to normal or gluten-free diet

Objective. Dermatitis herpetiformis (DH) is a cutaneous form of celiac disease affecting ∼17% of celiac disease patients. The aim was to determine how often celiac disease precedes the development of DH, and what is the impact of gluten-free diet (GFD) in this phenotype change. Material and methods. Our prospectively collected DH series from 1970 comprised 514 patients. We analyzed all DH patients who at least 2 years earlier had been diagnosed with celiac disease. DH diagnosis was confirmed by showing immunoglobulin A deposits in dermis. Serological and small bowel mucosal findings were analyzed, and the strictness of GFD treatment before and after the diagnosis of DH was evaluated. Results. Twenty (4%) DH patients had a prior diagnosis of celiac disease. The median time interval between celiac disease and DH detection was 9.5 years. Before DH appeared 4 patients had been on a normal gluten-containing diet, 10 had dietary lapses on a GFD, and 6 were on a strict GFD. Celiac autoantibodies were positive in 7 out of 19 patients, and 5 out of 7 undergoing small bowel biopsy had partial villous atrophy. Following DH diagnosis the rash was controlled after a median of 6 months on a strict GFD. Conclusions. Patients with celiac disease may develop DH by time. This is most often an indicator of poor adherence to GFD, and a rigorous dietary intervention is necessary. In the majority of cases, DH will be detected without prior celiac disease diagnosis, but the physicians should recognize this phenotype alteration.

Prevalence of Celiac Disease in Patients With Ocular Autoimmune Disease

Introduction: There have been recent reports about the association between celiac disease (CD) and ocular autoimmune disease (OAD), especially in Behcet’s patients. Although a moderately increased risk of OAD exists in patients with biopsy-proven CD, the prevalence of CD in OAD subjects remains unknown. Our aim was to investigate the prevalence of CD in a cohort of patients with non-infectious OAD from a tertiary uveitis center. Methods: With IRB approval and prior informed consent, we performed a cross-sectional study from 2012-2013. All patients with non-infectious OAD were included. Patients without a prior diagnosis of CD were checked for HLA-DQ2/DQ8 status, Ig A tissue transglutaminase antibody, and Ig A antiendomysial antibody, and were required to fill out a survey about gastrointestinal (GI) symptoms. Patients with a past history of infectious ocular disease were excluded. Demographics, type of ocular disease, and comorbidities were collected from each patient enrolled in the study. Results: This study included 124 patients (40 men and 84 women). Mean age was 46 years (range, 9-78 years). Most patients included were white (85%), had idiopathic uveitis (53.2%), and had anterior uveitis (40.3%). Forty-six percent of subjects were receiving immunomodulatory therapy (IMT) at the time of inclusion into the study. Four subjects had been diagnosed with CD by confirmatory biopsy prior to inclusion in our study. These patients did not fill out the survey and were not tested for CD autoantibodies. Out of 120 subjects tested serologically, 5 had positive serology for CD autoimmunity. Four of those subjects were HLA-DQ2-positive, and 1 subject was both HLA-DQ2 and DQ8-positive. From those with positive CD autoimmunity, 2 patients were biopsy-positive, 2 patients refused confirmatory biopsy, and 1 subject was biopsy-negative. Overall, 6 patients were identified as having biopsy proven-CD in our cohort of 124 patients, with a prevalence of 4.8. Although GI symptoms were very common in this series, 4 out of 5 subjects with positive serology were asymptomatic. Conclusion: Our study underlines the higher risk of CD in subjects with non-infectious OAD (around 5-fold greater prevalence in our series) compared to the general population. Identifying the presence of this association is critical because CD requires life-style modifying measures. Exclusion of gluten from the diet may help alleviate ocular symptoms without use of IMT, though further studies are needed. This study provides new epidemiological data and emphasizes the need of considering CD screening in patients with OAD without identified underlying etiology.

Predictors of dietary gluten avoidance in adults without a prior diagnosis of celiac disease

ObjectivePrior studies have shown that dietary gluten avoidance (DGA) is relatively common in children without previously diagnosed celiac disease (CD), and several clinical predictors of DGA have been found. However, available data on predictors of DGA in adults without diagnosed CD are limited. The aim of this study was to determine the independent predictors of DGA in this population. MethodsWe performed a structured medical record review of 376 patients, ages ≥20 y, who had never been formally diagnosed with CD, presenting for an initial CD evaluation (ICD-9-CM 579.0) between January 2000 and December 2010 at two large Boston teaching hospitals. We collected data including demographic characteristics, medical history, history of CD serology before referral, and self-reported DGA. Predictors of DGA were determined using multivariable logistic regression. ResultsMean age was 47 (SD = 17) years. We found that 41 patients (10.9%; 95% confidence interval [CI], 7.9–14.5) had avoided gluten at some time in their lives. Most patients had subjective abdominal complaints or bowel movement changes. History of CD seropositivity before referral was noted in 14%. Independent predictors of DGA (P < 0.05) were lactose intolerance (odds ratio [OR], 2.8; 95% CI, 1.1–7.5), food allergy (OR, 3.8; 95% CI, 1.04–13.7), and history of positive serology of less-specific CD markers before the referral (OR, 3.2; 95% CI, 1.3–7.9). ConclusionsGluten avoidance is common in a clinic population of adults without prior CD diagnosis. The recognized predictors suggest that DGA may associate with conditions presenting with nonspecific gastrointestinal complaints and perhaps with the perceived benefits of DGA among patients with prior history of positive CD serology.

Point-of-care testing for celiac disease has a low sensitivity in endoscopy

Celiac disease (CD) is a common but underdiagnosed condition. A rapid point-of-care test (POCT) could reduce lead times and missed diagnoses. To assess the utility of an immunoglobulin (Ig) A tissue transglutaminase (TTG) antibody POCT in an endoscopic setting. Prospective observational study. A single UK university hospital. Patients presenting with suspected CD, known CD, and routine endoscopy for upper GI symptoms. All patients were tested with POCT, serum TTG, endomysial antibody (EMA), and upper GI endoscopy with duodenal biopsies at the same visit. Comparison was made with histology in all cases, with villous atrophy regarded as diagnostic of CD. A total of 576 patients (63.5% female, mean [± standard deviation] age 49.7 years [± 17.6 years]) were recruited. A total of 523 patients had no prior diagnosis of CD, and 53 patients had known CD coming for reassessment. A total of 117 patients were newly diagnosed with CD, and 82 were positively identified by the POCT. Sensitivity, specificity, positive predictive value, and negative predictive value were 70.1%, 96.6%, 85.4%, and 91.8%, respectively. In comparison, TTG and EMA both performed significantly better than the POCT. Sensitivity and specificity of TTG were 91.0% and 83.5%, respectively, and EMA were 83.8% and 97.5%, respectively. Of patients with known CD coming for reassessment, 26 had villous atrophy, and POCT results were positive in 16 (61.5%). There was poor agreement between POCT and standard serology. High pre-test probability of CD. The performance of this POCT was disappointing compared with standard serology and cannot at present be recommended within the context of an endoscopy unit.

PTH-192 Once Negative always Negative? – the Clinical Utility of Repeating TTG

IntroductionPatients with chronic or recurrent abdominal symptoms, or anaemia, often undergo repeated rounds of investigations including tissue transglutaminase (TTG) antibody testing. The aim of this study was to investigate a)...

Celiac disease and microscopic colitis: A report of 4 cases

Celiac disease (CD) is an autoimmune disorder of the small intestine that occurs in genetically predisposed people at all ages. However, it can be associated also to other immunopathological disorders, and may be associated with abnormal histology in segments of the gut other than the small bowel including colonic inflammation. While guidelines for endoscopic investigation of the jejunum are well defined, no indication is defined for colonic investigation. We describe four cases of concurrent CD and microscopic colitis (MC) diagnosed at our department over a 10-year period and analyzed the main features and outcomes of CD in this setting. The symptoms of these patients were improved initially by a gluten-free diet before the onset of MC symptoms. Two of the patients were siblings and had an atypical form of CD. The other two patients with CD and MC also presented with fibrosing alveolitis and were anti-Saccharomyces cerevisiae antibody positive. The co-existence of immune-mediated small bowel and colonic inflammatory and pulmonary diseases are not well-known, and no systematic approach has been used to identify the lifelong patterns of these immune-based diseases. Patients can develop, or present with CD at any stage in life, which can co-exist with other gastrointestinal diseases of (auto-) immune origin. In addition, the familial co-existence and prevalence of MC in patients with a prior diagnosis of CD are unclear. Clinicians managing celiac disease should be aware of these associations and understand when to consider colon investigation.

Enteropathy-associated T-cell lymphoma in a patient without a prior diagnosis of celiac disease: A diagnostic conundrum

Enteropathy-associated T-cell lymphoma in a patient without a prior diagnosis of celiac disease: A diagnostic conundrum

M1189 Collagenous Sprue: Clinical Characteristics, Response to Steroids, and Prognosis

Background: Collagenous sprue (CS) is a very rare cause of severe malabsorption with an enteropathy that is characterized by villous atrophy and a distinctive band of subepithelial collagen deposition. A poor outcome has been reported historically. Aim: To describe the clinical characteristics, treatment, and prognosis in a contemporary cohort of patients with CS. Methods: We included cases with biopsy-proven CS evaluated at the Mayo Clinic Results: 15 patients (80% females) with a median age of 67 years (range, 53-83) were included. The clinical manifestations were diarrhea (100%), loss of weight (93%), and abdominal pain (14%). Hospitalizationwas required because severe diarrhea in 9 (64%) patients. Hypoalbuminemia and anemia were evident in 9 (64%) and 7 (50%) patients, respectively. Humanleukocyte antigen genes DQ2 or DQ8 were present in 12 (80%) patients (DQ2+ single dose [n=8], DQ2+ double dose [n=3], and DQ2+/DQ8+ [n=1]). Celiac antibodies were present in only 1 patient. A prior diagnosis of celiac disease was evident in 7 (47%) patients. Histologically, all cases had both the abnormal collagen deposition and some degree of villous atrophy. Aberrant (clonal) intraepithelial lymphocytes were detected in 1 (of 12) patients tested by both immunostaining and T-cell clonality analysis. Associated disorders were collagenous gastritis (n=4), collagenous colitis (n=4), small-intestine bacterial overgrowth (n=4), lymphocytic colitis (n=2), lymphocytic gastritis (n=1), autoimmune hepatitis (n=1), and hyposplenism (n=1). All patients received treatment with a combination of a strict gluten-free diet and steroids such as budesonide 9mg/day (n=12), prednisone 30-40 mg/day (n=2) and dexamethasone 8 mg/day (n=1). Parenteral nutrition was necessary in 11 (79%) patients. One patient developed enteropathy-type T-cell lymphoma during followup and received a combination of nitrogen mustard and methylprednisolone. Clinical followup after treatment was available in 12 (92%) patients (median time = 16 months; range, 172), disappearance of diarrhea was observed in 11 with complete histologic remission documented in one case. Three patients died during follow-up because of emaciation, enteropathy-type T-cell lymphoma, and aspiration pneumonia, respectively. Conclusions: We report the largest case series of CS. Treatment with a combination of gluten-free diet and steroids (especially budesonide) was useful to control symptoms in most patients; however, length of follow-up was limited so far to a few months in the majority of our patients. CS was associated with collagen deposition in other organs, autoimmune conditions, and lymphoma.

M1190 Natural History of Eosinophilic Gastroenteritis

Background: Collagenous sprue (CS) is a very rare cause of severe malabsorption with an enteropathy that is characterized by villous atrophy and a distinctive band of subepithelial collagen deposition. A poor outcome has been reported historically. Aim: To describe the clinical characteristics, treatment, and prognosis in a contemporary cohort of patients with CS. Methods: We included cases with biopsy-proven CS evaluated at the Mayo Clinic Results: 15 patients (80% females) with a median age of 67 years (range, 53-83) were included. The clinical manifestations were diarrhea (100%), loss of weight (93%), and abdominal pain (14%). Hospitalizationwas required because severe diarrhea in 9 (64%) patients. Hypoalbuminemia and anemia were evident in 9 (64%) and 7 (50%) patients, respectively. Humanleukocyte antigen genes DQ2 or DQ8 were present in 12 (80%) patients (DQ2+ single dose [n=8], DQ2+ double dose [n=3], and DQ2+/DQ8+ [n=1]). Celiac antibodies were present in only 1 patient. A prior diagnosis of celiac disease was evident in 7 (47%) patients. Histologically, all cases had both the abnormal collagen deposition and some degree of villous atrophy. Aberrant (clonal) intraepithelial lymphocytes were detected in 1 (of 12) patients tested by both immunostaining and T-cell clonality analysis. Associated disorders were collagenous gastritis (n=4), collagenous colitis (n=4), small-intestine bacterial overgrowth (n=4), lymphocytic colitis (n=2), lymphocytic gastritis (n=1), autoimmune hepatitis (n=1), and hyposplenism (n=1). All patients received treatment with a combination of a strict gluten-free diet and steroids such as budesonide 9mg/day (n=12), prednisone 30-40 mg/day (n=2) and dexamethasone 8 mg/day (n=1). Parenteral nutrition was necessary in 11 (79%) patients. One patient developed enteropathy-type T-cell lymphoma during followup and received a combination of nitrogen mustard and methylprednisolone. Clinical followup after treatment was available in 12 (92%) patients (median time = 16 months; range, 172), disappearance of diarrhea was observed in 11 with complete histologic remission documented in one case. Three patients died during follow-up because of emaciation, enteropathy-type T-cell lymphoma, and aspiration pneumonia, respectively. Conclusions: We report the largest case series of CS. Treatment with a combination of gluten-free diet and steroids (especially budesonide) was useful to control symptoms in most patients; however, length of follow-up was limited so far to a few months in the majority of our patients. CS was associated with collagen deposition in other organs, autoimmune conditions, and lymphoma.

Coeliac disease and body mass index: A study of two Swedish general population-based registers

Objective. To examine the relationship between body mass index (BMI) and an inpatient diagnosis of coeliac disease (CD) in two independent Swedish national registers. Material andmethods. Study 1: Cohort study of women. The relationship between (pre-pregnancy) BMI and CD in pregnant women was evaluated (174 undiagnosed CD (at time of pregnancy), 550 diagnosed CD, 787,986 without a diagnosis of CD). The association between BMI and undiagnosed CD was estimated by Cox regression. Study 2: Case-control study of men. The relationship between BMI and CD in male conscripts was evaluated (70 undiagnosed CD, 1,047 diagnosed CD and 6,887 without a diagnosis of CD). The association between BMI and undiagnosed CD was estimated by logistic regression. Prevalence of underweight, normal weight and overweight was compared between diagnosed CD, undiagnosed CD and no diagnosis of CD. Results. The prevalence of underweight (BMI <18.5) in women was: reference individual: 5.2%; undiagnosed CD: 16.7% and prior diagnosis of CD: 6.4%. In men, the corresponding figures were 6.5%; 14.3% and 9.8%, respectively. Underweight was associated with undiagnosed CD (future diagnosis of CD) in both women (hazard ration (HR) = 2.5; 95% CI = 1.6–3.7) and men (odds ratio (OR) = 2.4; 95% CI = 1.2–4.9). In women, overweight was negatively associated with undiagnosed CD (HR = 0.6; 95% CI = 0.4–0.9), but not in men (OR = 1.1; 95% CI = 0.6–2.2). 9.2% of women with undiagnosed CD and 14.3% of men with undiagnosed CD were overweight. Conclusions. Underweight individuals are at increased risk of having undiagnosed CD. However, overweight does not rule out CD.

Gastrointestinal Tract Pathology in Patients With Common Variable Immunodeficiency (CVID)

Common variable immunodeficiency (CVID) is characterized by a host of gastrointestinal (GI) lesions that can mimic other conditions. We reviewed clinical documentation and samples from 132 separate GI biopsy or resection sites on 20 CVID patients obtained over a 26-year period, including biopsies from the colon (34), esophagus (19), small intestine (38), and stomach (35), a partial gastrectomy, small bowel resection, colectomy, 2 cholecystectomies, and 1 appendectomy. There were 13 males and 7 females. Nine patients were children (10 y and younger) and 11 were adults. Age at diagnosis ranged from 6 months to 62 years (median, 35.5 y), and age at biopsy ranged from 10 months to 67 years (median, 38 y). Esophageal samples often showed intraepithelial neutrophils, accompanied by candida. Half of patients' esophageal biopsies had prominent intraepithelial lymphocytosis, one of which also had prominent apoptosis. The stomachs of 67% of patients lacked plasma cells. Most showed lymphoid aggregates. An increase in apoptosis was detected in biopsies from a third. About 20% had a lymphocytic gastritis pattern. Intraepithelial neutrophils were found in a subset, accompanied by various infections [cytomegalovirus (CMV), Helicobacter pylori, and Cryptosporidium]. Granulomas were found in 1 patient. Gastric adenocarcinoma was identified in one patient. There was a paucity of small bowel plasma cells in the majority of patients (68%). The small bowel showed prominent lymphoid aggregates in about half (47%). An increase in apoptosis was detected in specimens from about 20%. Increased intraepithelial lymphocytes (IELs) were found in samples from over half of patients (63%), most of whom (83%) also had villous blunting, mimicking celiac disease. Intraepithelial neutrophils were found in a subset (32%) and correlated with CMV and Cryptosporidium infections. Granulomas were seen in biopsies from 2 patients (11%). One patient had a collagenous enteritis pattern (accompanied by a collagenous colitis pattern). One patient had autoimmune enteritis; biopsies from this patient were initially relatively normal but later displayed prominent crypt apoptosis and loss of goblet cells. In colon samples, a paucity of plasma cells was seen in 10 patients (63%). The colon showed lymphoid aggregates in most patients (81%). Apoptosis was prominent in samples from half of the patients (50%). Biopsies from 6 patients had a lymphocytic colitis pattern (38%) and 2 patients had a collagenous colitis pattern. Intraepithelial neutrophils were found in samples from most patients (88%). Crypt distortion was seen in 6 of these patients (43%), thereby mimicking ulcerative or Crohn colitis. Granulomas were found in 3 patients (19%). CMV was detected in 1 patient. The appendix from 1 patient showed Cryptosporidium and acute serositis with a paucity of plasma cells and an increase in apoptosis. The gallbladder from 1 patient showed acute cholecystitis, and another patient's gallbladder lacked plasma cells. GI tract CVID displays a wide spectrum of histologic patterns. Its features can mimic lymphocytic colitis, collagenous enterocolitis, celiac disease, lymphocytic gastritis, granulomatous disease, acute graft-versus-host disease, and inflammatory bowel disease. In fact, in our series, we found patients with a prior diagnosis of celiac disease (25%) and inflammatory bowel disease (35%), including Crohn disease (15%). The diagnosis of CVID may be suspected on the basis of the lack of plasma cells in a GI biopsy, but because this feature is only present in about two-thirds of patients, the diagnosis cannot always be suggested in isolation of other clinical and laboratory findings.

CHOP plus Alemtuzumab can Induce Metabolic Response by FDG-PET but has Minimal Long-term Benefits: A Case Report and Literature Review

Enteropathy-associated T-cell lymphoma (EATL) is a rare subtype of non-Hodgkin's lymphoma characterized by an aggressive phenotype and poor outcome in the vast majority of cases. Substantial portions of patients have either no prior diagnosis of celiac disease or have a subacute course of celiac disease followed by EATL diagnosis. We report a case of a 72-year-old African American male without history of gastrointestinal intolerance who presented with acute abdominal pain and weight loss leading to the eventual diagnosis of gastric EATL. Despite an initial promising clinical and radiographic response to cyclophosphamide, doxorubicin, vincristine, and prednisone plus alemtuzumab, the disease rapidly progressed with a fatal outcome. This case and review of the literature highlights the features of this uncommon disease and addresses both the diagnostic and therapeutic challenges of this aggressive malignancy. We also discuss our experience with the use of fluoro-2-deoxy-D-glucose positron emission tomography in monitoring treatment response.