Clinical features and diagnosis of celiac disease

Celiac disease is a life-long enteropathy caused by an intolerance to gluten. The pathologic lesion of the small intestinal mucosa is characterized by the loss of absorptive villi, crypt cell hyperplasia, and infiltration of the lamina propria with inflammatory cells. The clinical presentation of celiac disease varies greatly depending on patient's age, duration and extent of the disease, and the presence of extraintestinal manifestations. The classical symptoms like diarrhea, weight loss and abdominal pain are seen less common. Unfortunately, most patients with celiac disease have either silent or atypical presentations, thus escaping diagnosis for several years. The pathologic changes and symptoms resolve when gluten is excluded from the diet for a sustained period. Untreated celiac disease is associated with significant risk of the development of enteropathy-associated intestinal lymphoma.     

Einheimische Sprue (Zöliakie)

Celiac disease is a life-long enteropathy caused by an intolerance to gluten. The pathologic lesion of the small intestinal mucosa is characterized by the loss of absorptive villi, crypt cell hyperplasia, and infiltration of the lamina propria with inflammatory cells. The clinical presentation of celiac disease varies greatly depending on patient’s age, duration and extent of the disease, and the presence of extraintestinal manifestations. The classical symptoms like diarrhea, weight loss and abdominal pain are seen less common. Unfortunately, most patients with celiac disease have either silent or atypical presentations, thus escaping diagnosis for several years. The pathologic changes and symptoms resolve when gluten is excluded from the diet for a sustained period. Untreated celiac disease is associated with significant risk of the development of enteropathy-associated intestinal lymphoma.     

Etiology of nonresponsive celiac disease: results of a systematic approach

OBJECTIVES: Nonresponse or relapse of symptoms is common in patients with celiac disease treated with gluten free diet. Refractory sprue (RS) is defined as initial or subsequent failure of a strict gluten-free diet to restore normal intestinal architecture and function in patients who have celiac-like enteropathy. The aims of this study were: 1) to identify causes of persistent symptoms in patients referred with presumed diagnosis of nonresponsive celiac disease (NCD); and 2) to characterize patients with true RS. METHODS: Patients were identified who had been systematically evaluated for NCD between January 1997, and May 2001. Patient records and small bowel biopsy results were reviewed. RESULTS: A total of 55 patients were referred with a presumed diagnosis of NCD. Six did not have celiac disease and had other diseases responsible for their symptoms. Diarrhea, abdominal pain, and weight loss were the most common reasons for evaluation in cases of NCD, whereas weight loss, steatorrhea, and diarrhea were the most common presenting features of RS (nine patients). Of the 49 patients with celiac disease, 25 were identified as having gluten contamination. Additional diagnoses accounting for persistent symptoms included: pancreatic insufficiency, irritable bowel syndrome, bacterial overgrowth, lymphocytic colitis, collagenous colitis, ulcerative jejunitis, T-cell lymphoma, pancreatic cancer, fructose intolerance, protein losing enteropathy, cavitating lymphadenopathy syndrome, and tropical sprue. CONCLUSIONS: Based on this study, we conclude the following: 1) gluten contamination is the leading reason for NCD; 2) of NCD cases, 18% are due to RS; and 3) alternative diseases or those coexistent with celiac disease and gluten contamination should be ruled out before a diagnosis of RS is made.     

Role of pancreatic impairment in growth recovery during gluten-free diet in childhood celiac disease

BACKGROUND & AIMS: Clinical significance and duration of insufficient release of pancreatic enzymes in childhood celiac disease have not been clarified. The aim of this study was to evaluate the role that pancreatic impairment plays in growth recovery and the duration of this impairment. METHODS: Forty-six patients with celiac disease who had a median age of 2.5 years were enrolled. Fecal chymotrypsin level was determined at diagnosis and then every 15 days after the beginning of a gluten-free diet in all patients. RESULTS: At diagnosis, 17 of 46 patients with celiac disease had subnormal fecal chymotrypsin values. During the gluten-free diet, a progressive reduction in the percentage of patients with subnormal fecal chymotrypsin values was observed: 12 of 46 patients after 30 days and 2 of 46 patients after 60 days. Weight increase after 2 months of gluten-free diet was significantly greater in patients with normal fecal chymotrypsin values at diagnosis than in patients with subnormal values, and a positive correlation was found between fecal chymotrypsin at diagnosis and weight increase (r = 0.56). CONCLUSIONS: A small percentage of patients with celiac disease still had subnormal chymotrypsin concentrations after 60 days of gluten-free diet. Fecal chymotrypsin is a predictive index of weight recovery in the first months after diagnosis of celiac disease; it could be used to select patients for enzyme supplementation therapy. (Gastroenterology 1997 Jun;112(6):1839-44)     

The Canadian Celiac Health Survey

The purpose of this study was to characterize the diagnostic process, frequency of associated disorders, family history, and impact of a gluten-free diet in individuals with celiac disease. All members of the Canadian Celiac Association (n=5240) were surveyed with a questionnaire. Respondents included 2681 adults with biopsy-proven celiac disease. The mean age was 56 years. Most common presenting symptoms included abdominal pain (83%), diarrhea (76%), and weight loss (69%). The mean delay in diagnosis was 11.7 years. Diagnoses made prior to celiac disease included anemia (40%), stress (31%), and irritable bowel syndrome (29%). Osteoporosis was common. Prior to diagnosis, 27% of respondents consulted three or more doctors about their symptoms. Delays in diagnosis of celiac disease remain a problem. Associated medical conditions occur frequently. More accurate food labeling is needed. Improved awareness of celiac disease and greater use of serological screening tests may result in earlier diagnosis and reduced risk of associated conditions.     

Massive Hepatic Steatosis Complicating Adult Celiac Disease: Report of a Case and Review of the Literature

Hepatomegaly, chronic diarrhea, and weight loss in a middle-aged woman were found to be due to massive hepatic steatosis and adult celiac disease. After she was on a gluten-free diet for 1 yr, improvement in clinical, laboratory, and pathological parameters was witnessed. Massive hepatic steatosis complicating adult celiac disease is an uncommon occurrence, differing from other, more frequently encountered hepatopathies in this disease, insofar as pathogenetic and prognostic aspects are concerned.     

A rare cause of mesenteric ischemia: celiac axis compression syndrome

Mesenteric ischemia is an uncommon etiology of abdominal pain. Celiac axis compression syndrome is an extremely rare cause of mesenteric ischemia. The primary pathological mechanism is the external compression of the celiac trunk by median arcuate ligament. The clinical manifestation of celiac axis compression syndrome includes postprandial pain, diarrhea, and body weight loss. The diagnosis of this disease is usually difficult and depends on the angiography findings. For treatment, only percutaneous transluminal angioplasty and surgical intervention have been suggested in reviews in the literature. We, herein, report an unusual case of celiac axis compression syndrome and also review the literature pertaining to this disease.     

Chronic urticaria: a cutaneous manifestation of celiac disease.

Celiac disease, or gluten-sensitive enteropathy, is an immune-mediated disease of the small bowel that results in malabsorption. It classically presents with gastrointestinal symptoms including chronic diarrhea, weight loss, abdominal bloating and anorexia. It is becoming more frequently identified in asymptomatic patients with a diagnosis of deficiencies related to malabsorption of iron, folic acid, vitamin B12 and vitamin D. It is increasingly identified as a cause for early or refractory osteoporosis. Occasionally, celiac disease presents with cutaneous manifestations alone. Dermatitis herpetiformis is a well-recognized cutaneous manifestation of celiac disease. Other cutaneous manifestations include alopecia, angular stomatitis and aphthous ulcerations. Described here is a case of a 24-year-old woman who presented with intermittent urticaria and gastrointestinal complaints. She was found to have celiac disease on small-bowel biopsy. Both her gastrointestinal symptoms and urticaria resolved when she was put on a gluten-free diet, suggesting that her urticaria was a cutaneous manifestation of celiac disease.     

Celiac crisis in an adult type 1 diabetes mellitus patient presented with diarrhea,weight loss and hypoglycemic attacks

Type 1 diabetes mellitus (T1DM) is an autoimmune disease, characterized by loss of the insulin-producing β cells of the islets of Langerhans in the pancreas, causing insulin deficiency. Celiac disease has been seen in 3 to 8 % of T1DM patients. Celiac crisis, an acute severe onset of celiac disease, is a rare and life-threatening manifestation. We report a 50-year-old man with type 1 diabetes mellitus who arrived at our service with a 2-month history of watery diarrhea associated with hypoglycemic attacks, abdominal pain, and weight loss of 13 kg. The diagnosis of celiac crisis was made based on diarrhea leading to dehydration, severe metabolic and electrolyte abnormalities, and subsequent improvement after introduction of a gluten-free diet.     

Non-classical clinical presentation at diagnosis by male celiac disease patients of older age

Background. In a biopsy-proven adult celiac disease (CeD) cohort from the Netherlands, male patients were diagnosed with CeD at significantly older ages than female patients.ObjectivesTo identify which factors contribute to diagnosis later in life and whether diagnostic delay influences improvement of symptoms after starting a gluten-free diet (GFD).Methods. We performed a questionnaire study in 211 CeD patients (67:144, male:female) with median age at diagnosis of 41.8 years (interquartile range: 25–58) and at least Marsh 2 histology.Results. Classical symptoms (diarrhea, fatigue, abdominal pain and/or weight loss) were more frequent in women than men, but sex was not significantly associated with age at diagnosis. In a multivariate analysis, a non-classical presentation (without any classical symptoms) and a negative family history of CeD were significant predictors of older age at diagnosis (coefficients of 8 and 12 years, respectively). A delay of >3 years between first symptom and diagnosis was associated with slower improvement of symptoms after start of GFD, but not with sex, presentation of classical symptoms or age at diagnosis.Conclusion. Non-classical CeD presentation is more prevalent in men and is associated with a diagnosis of CeD later in life. Recognizing CeD sooner after onset of symptoms is important because a long diagnostic delay is associated with a slower improvement of symptoms after starting a GFD.     

Presentations of adult celiac disease in a nationwide patient support group

Recent epidemiological studies primarily from Europe document that adult celiac disease often lacks the classic presentation of steatorrhea and weight loss. There are few surveys of adult celiac disease in the United States. We surveyed the large population of a nationwide patient support group to determine their disease presentations. In the initial survey (N = 1032 respondents), the median age at onset was 46 years, and the diagnosis of adult celiac disease was often delayed (median 12 months, with 21% delayed over 10 years). Only 32% of adults were underweight, and only about 50% reported frequent diarrhea and weight loss. A second survey documented that common presenting symptoms were fatigue (82%), abdominal pain (77%), bloating or gas (73%), and anemia (63%). Initial physician diagnoses were often irritable bowel syndrome (37%), psychological disorders (29%), and fibromyalgia (9%). These initial presentations are similar to those in Europe and often resemble irritable bowel syndrome.     

Overweight in celiac disease: prevalence, clinical characteristics, and effect of a gluten-free diet

BACKGROUND: It is well established that a minority of celiac patients present with "classic" symptoms due to malabsorption. However, few studies have focussed on the distribution of body mass index (BMI) in celiac populations and its relationship to clinical characteristics, or on its response to treatment. METHODS: We reviewed BMI measurements and other clinical and pathological characteristics from a database of 371 celiac patients diagnosed over a 10-yr period and seen by a single gastroenterologist. To assess response to gluten exclusion, we compared BMI at diagnosis and after 2 yr treatment in patients with serological support for dietary compliance. RESULTS: Mean BMI was 24.6 kg/m2 (range 16.3-43.5). Seventeen patients (5%) were underweight (BMI < 18.5), 211 (57%) were normal, and 143 (39%) were overweight (BMI > or = 25), including 48 (13% of all patients) in the obese range (BMI > or = 30.0). There was a significant association between low BMI and female gender, history of diarrhea, reduced hemoglobin concentration, reduced bone mineral density (BMD), osteoporosis, and higher grades (subtotal/total) of villous atrophy. Of patients compliant with a gluten-free diet, 81% had gained weight after 2 yr, including 82% of initially overweight patients. CONCLUSIONS: Few celiac patients are underweight at diagnosis and a large minority is overweight; these are less likely to present with classical features of diarrhea and reduced hemoglobin. Failed or delayed diagnosis of celiac disease may reflect lack of awareness of this large subgroup. The increase in weight of already overweight patients after dietary gluten exclusion is a potential cause of morbidity, and the gluten-free diet as conventionally prescribed needs to be modified accordingly.     

Eosinophilic esophagitis in children with celiac disease

Background and Aims:  Eosinophilic esophagitis and celiac disease are distinct gastrointestinal disorders. The present study in children highlights the possible coexistence of these two conditions. This study also analyzes the epidemiological and clinical profiles of these patients.
Methods:  The medical records of patients diagnosed with celiac disease from 1 April 1999 to 31 March 2007 were reviewed. Patients with coincident histological diagnosis of eosinophilic esophagitis were retrospectively identified. The presenting symptoms, laboratory evaluations, endoscopic and histopathological findings, and treatment and follow-up outcomes of these patients were analyzed.
Results:  Of the 221 patients with celiac disease, seven (3.2%) were also diagnosed with eosinophilic esophagitis. A majority (6/7) presented with periumbilical pain and diarrhea. None had dysphagia. Each patient had abnormal celiac screening tests. Three patients had peripheral blood eosinophilia and elevated eosinophil cationic protein. Endoscopic changes of eosinophilic esophagitis and celiac disease were apparent in the majority of patients (6/7). A gluten-free diet was instituted in every patient. Topical corticosteroid therapy was started in one patient at diagnosis and in another patient after repeat endoscopic and histopathological evaluations.
Conclusions:  Awareness of the potential coexistence of eosinophilic esophagitis and celiac disease should promote optimal diagnosis of these conditions. Routine esophageal biopsies may be warranted when investigating for celiac disease.     

Profile of chronic small-bowel diarrhea in adults in Western India: a hospital-based study.

BACKGROUND: Small-bowel diarrhea is reported to account for 10% of all cases of chronic diarrhea. Data on the etiology and clinical presentation of chronic small-bowel diarrhea in adult Indians is scarce. METHODS: 50 patients (mean age 32.8 years; 26 men) with chronic small bowel diarrhea were evaluated clinically, and investigated to determine etiology. The diagnosis of small-bowel diarrhea was based on history, stool volume and associated symptoms. RESULTS: Abdominal pain (n=22, 44%) and weight loss (n=37, 74%) were the most common symptoms, apart from diarrhea. Anemia (70%) and hypoalbuminemia (48%) were other important biochemical abnormalities. Intestinal tuberculosis (26%) and celiac disease (26%) were the most common causes of chronic small-bowel diarrhea. CONCLUSION: Tuberculosis of intestine and celiac disease are common causes of small-bowel diarrhea in our population. Tropical sprue seems to be a rare cause.     

The usefulness of routine small bowel biopsies in evaluation of iron deficiency anemia

BACKGROUND: Iron deficiency anemia (IDA) may be the sole manifestation of celiac disease. The role of routine small bowel biopsies obtained during endoscopy in the evaluation of IDA is unclear. This study assessed the usefulness of routine small bowel biopsies in patients presenting with IDA. STUDY: Evaluation of 103 consecutive patients with IDA undergoing panendoscopy with routine small bowel biopsies was performed. All patients had a diagnosis of IDA with either a ferritin less than 15 microg/L or iron saturation less than 8%. Celiac disease was defined as total or partial villous atrophy with intraepithelial lymphocytosis, histologically, and a clinical response to gluten free diet. Gastrointestinal symptoms were recorded. RESULTS: Nine patients (8.7%) were diagnosed with celiac disease. Of these patients, endoscopic lesions potentially responsible for IDA were found in 33%. We found no statistically significant difference when comparing reports of diarrhea, weight loss, abdominal pain, nausea or vomiting, aspirin or NSAID use, or menopausal status with celiac disease status. CONCLUSIONS: Routine small bowel biopsies to evaluate for celiac disease are indicated in the evaluation of patients with IDA. The finding of endoscopic lesions that may otherwise explain IDA should not preclude small bowel biopsy.     

Prevalence and clinical profile of celiac disease in type 1 diabetes mellitus in north India

Background and Aim: There is scanty data on the occurrence of celiac disease in patients with type 1 diabetes mellitus in South Asia. Our aim was to study the prevalence and clinical profile of celiac disease in patients with type 1 diabetes mellitus in a tertiary care referral centre in north India. Methods: Consecutive patients of type 1 diabetes mellitus attending the Endocrine clinic of our institute between January 2002 and December 2008 were screened using anti‐tissue transglutaminase antibodies (tTGAb), and those positive were subjected to duodenal biopsy. Clinical profile of these patients was recorded. Results: Out of 189 patients of type 1 diabetes mellitus, 21 (11.1%) were diagnosed to have celiac disease on the basis of positive serology (tTGAb) and duodenal histology. The mean age at diagnosis of diabetes was 10.81 ± 7.3 years and that of celiac disease was 13.74 ± 5.71 years, with a difference of 5.18 ± 4.75 years between the two. Only 2/21 patients with celiac disease had been diagnosed before detection of diabetes mellitus. Short stature was the commonest (52.3%) manifestation of celiac disease, followed by anemia (47.3), weight loss (42.8%), diarrhea (28.6%) and abdominal pain (14.2%). After initiating gluten free diet, 14/16 symptomatic patients had reversal of anemia, weight loss and diarrhea. Growth rate velocity improved from 2.3 ± 1.0 cm/year to 5.5 ± 2.4 cm/year in those with short stature. Conclusion: Celiac disease is highly prevalent in patients with type 1 diabetes mellitus (11.1%) and majority of them (90.5%) were diagnosed on screening. Routine screening is required for early diagnosis and combat associated co‐morbidities.     

Use of anti tumor necrosis factor-alpha monoclonal antibody for ulcerative jejunoileitis

Ulcerative jejunoileitis is an uncommon clinical syndrome consisting of abdominal pain,weight loss associated with diarrhea,and multiple inflammatory ulcerations and strictures of the small bowel.Ulcerative jejunoileitis can complicate established celiac disease or develop in patients de novo.Increased levels of tumor necrosis factor-alpha(TNF-α) in the small intestine of patients with untreated celiac disease are associated with a role in the immune pathogenesis of this disorder.No specific therapy has been shown to change the course of ulcerative jejunoileitis.We report a case of severe ulcerative jejunoileitis previously unresponsive to traditional therapies,including high dose corticosteroids and cyclosporine.The patient had a dramatic resolution of symptoms and a complete normalization of endoscopic findings after anti-TNF-α monoclonal antibody,infliximab(Remicade).     

Diagnosis of celiac disease

In spite of modern diagnostic possibilities, the diagnosis of celiac disease is still challenging for the physician. This is due to the great variability of the clinical presentation. Nowadays, the classical symptoms like diarrhea, weight loss and abdominal pain are seen less often. It has become evident that celiac disease is not merely a disease of the intestine but of the entire organism. Furthermore, extraintestinal manifestations can present without any gastrointestinal symptoms. It is likely that in many cases the immune system and not nutrient deficiencies play a major role. In addition, the diagnostic tests are not always unequivocal. There is a great variability of the small intestinal changes which are sometimes in contradiction to the antibody results. Since celiac disease implies a lifelong gluten-free diet, a firm diagnosis should be obtained. Thus, one should not rely on a single test but should rather consider serology, histology and clinical response altogether.     

Celiac disease in South-West of Iran

AIM: Celiac disease is characterized by life-long gluten intolerance. Clinical features of patients with celiac disease are variable. Studies about the prevalence of celiac disease in our country are scarce and there is no study on the prevalence of celiac disease in southern Iran. In the current study, clinical, laboratory and histological features of 52 patients with celiac disease were evaluated. METHODS: In a cross sectional study we retrospectively studied the characteristics of 52 celiac patients at Ahwaz JundiShapour University Hospitals (AJSUH) from November 1, 1999 to 1st Sep 2004. Intestinal biopsy and serum antigliadin and anti-endomysium antibodies were used for the diagnosis of patients. Mucosal lesions were classified according to the criteria of Marsh. Antigliadin antibodies were measured with a commercial enzyme-linked immunosorbent assay. Anti-endomysium antibodies were analyzed by indirect immunofluorescence with the use of a section of monkey esophagus. Routine hematological and biochemical analyses and measurement of immunoglobulin levels were undertaken. RESULTS: Male: female ratio was 1.08. The mean±SD patient age was 21±4.5 years (range 10-70 years) and the most common symptoms were diarrhea and weight loss (78.8%) followed by fatigue (73.1%), pallor (65.4%), anorexia (40.4%), abdominal distention (32.7%), and failure to thrive (23.1%). Diarrhea and weight loss and fatigue were the most common findings. Iron deficiency anemia was found in 63.2% of patients and this became normal after adoption of a gluten-free diet in all patients. Immunoglobulin A, IgG antigliadin antibodies and IgA anti-endomysium antibodies were found in 33 and 48 cases, 78.8% and 85.4% of patients, respectively. Biopsy of the small intestine revealed that 90.4% of patients had typical lesions according to the Marsh classification. CONCLUSION: Although classical presentation was seen in most of the patients, atypical clinical manifestations of celiac disease should be kept in mind. In particular, patients with uncommon findings, such as short stature, and iron-deficiency anemia, should be screened for celiac disease. Further epidemiological studies in our area in the general population and in high risk groups seem to be indicated.     

Diarrhea in a patient with Down syndrome and endemic sprue

BACKGROUND: Down syndrome is associated with disorders such as celiac disease, hypothyroidism, and insulin-dependent diabetes mellitus. In patients with mono- or oligosymptomatic celiac disease the time interval between the onset of symptoms and diagnosis often is unacceptably long. CASE REPORT: A female patient with Down syndrome is presented who had acute watery diarrhea, which spontaneously ceased but recurred after a few days. After endoscopic and histologic evaluation and measurement of gliadin, endomysium, and reticulin antibodies celiac sprue was diagnosed. Further investigation showed findings of autoimmune hypothyroidism and secondary hyperparathyreoidism. After the patient was put on a gluten-free diet her state quickly improved. CONCLUSION: Associations between Down syndrome and autoimmune diseases exist. Patients with acute gastrointestinal symptoms should be evaluated as to celiac disease. The time interval between the onset of symptoms and diagnosis of celiac disease can be shortened, if all diagnostic tools are used at the appropriate time.