Hepatobiliary and pancreatic disorders in celiac disease

A variety of hepatic and biliary tract disorders may complicate the clinical course of celiac disease. Some of these have been hypothesized to share common genetic factors or have a common immunopathogenesis, such as primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune forms of hepatitis or cholangitis. Other hepatic changes in celiac disease may be associated with malnutrition resulting from impaired nutrient absorption, including hepatic steatosis. In addition, celiac disease may be associated with rare hepatic complications, such as hepatic T-cell lymphoma. Finally, pancreatic exocrine function may be impaired in celiac disease and represent a cause of treatment failure.     

Dermatomyositis associated with celiac disease: response to a gluten-free diet.

The association between dermatomyositis and celiac disease in children has been well documented. In the adult population, however, the association has not been clearly established. A rare case of concomitant dermatomyositis and celiac disease in a 40-year-old woman is presented. After having been diagnosed with dermatomyositis and iron deficiency anemia, this patient was referred to the gastroenterology clinic to exclude a gastrointestinal malignancy. Blood tests revealed various vitamin deficiencies consistent with malabsorption. The results of gastroscopy with duodenal biopsy were consistent with celiac disease. After she was put on a strict gluten-free diet, both nutritional deficiencies and the dermatomyositis resolved. The patient's human leukocyte antigen haplotype study was positive for DR3 and DQ2, which have been shown to be associated with both juvenile dermatomyositis and celiac disease. It is suggested that patients with newly diagnosed dermatomyositis be investigated for concomitant celiac disease even in the absence of gastrointestinal symptoms.     

The patient with unexplained elevated serum liver enzymes

The pattern of elevated serum liver enzymes in symptomatic or asymptomatic patients allows for an initial classification of liver diseases into cholestatic or hepatocellular diseases. A female patient with extrahepatic cholestasis due to segmental bile duct strictures and a localized mass lesion within the pancreas is presented. Although many diagnostic procedures were performed in this case the diagnosis was not obtained before surgical laparotomy was initiated with bioptic sampling from bile ducts, lymph nodes and pancreatic tissue. Microscopic examination of the specimen revealed extensive biliary and pancreatic scarring together with periductal infiltrates composed of lymphocytes and plasma cells consistent with sclerosing cholangitis in systemic autoimmune pancreatitis. The patient completely recovered upon treatment with prednisone and azathioprine. The difficult approach to the final diagnosis is discussed in light of established and modern diagnostic tools.     

Raised serum concentrations of pancreatic enzymes in cigarette smokers.

Circulating concentrations of digestive enzymes, certain lysosomal hydrolases and protease inhibitors were measured in 19 heavy smokers and 13 non-smokers before (basal) and at 15, 30, and 60 minutes after a single intravenous injection of secretin (75 CU). In smokers, basal serum amylase and immunoreactive pancreatic elastase 2 (IRE2) concentrations were about 100% and 25% higher respectively, than in the non-smokers, whereas, no differences were observed in basal immunoreactive cationic trypsinogen (IRCT) concentrations and in acid phosphatase and beta-glucuronidase activities between the two groups. Furthermore, a single injection of secretin to cigarette smokers significantly increased serum amylase, IRCT and IRE2 by 155%, 200%, and 100%, respectively when compared with their corresponding basal levels. No such increment was observed in the non-smokers. In addition, there were no significant differences in serum trypsin or elastase inhibitory capacity or immunoreactive alpha 1-protease inhibitor and alpha 2-macroglobulin levels between smokers and non-smokers. The levels and inhibitory capacity of these protease inhibitors was also not affected by secretin injection. These data suggest that cigarette smoking enhances the responsiveness of the exocrine pancreas to a physiological stimulus such as secretin, with resultant substantial increase in the concentrations of pancreatic hydrolases in blood.     

Screening for celiac disease in non-Hodgkin's lymphoma patients: a serum anti-transglutaminase-based approach

Several studies have shown the existence of an association between celiac disease (CD) and non-Hodgkin's lymphoma (NHL). Our aim was to evaluate the usefulness of the serum anti-tissue transglutaminase (anti-tTG) antibody assay in screening for CD in consecutive NHL patients. In all, 80 consecutive patients (median age 61 years) with a new diagnosis of NHL were included. To compare the frequency of CD and of positive results for the anti-tTG assay, we enrolled 500 blood donors. In all patients serum anti-tTG was determined with two different ELISA: one based on tTG from guinea pig (gp-tTG) and the other based on human recombinant t-TG (h-tTG) as the antigens. Serum anti-endomysial antibodies (EmA) were also assayed. Subjects with positive serum EmA and/or anti-tTG underwent intestinal biopsy for histology study, HLA-DQ phenotype determination, and serum anti-gliadin (AGA) assay. Eight of 80 (10%) NHL patients were positive for anti-tTG ELISA—two of these exclusively for anti-gp-tTG and six for anti-h-tTG (7.5%). None of the 80 NHL patients were positive for serum EmA. The frequency of anti-tTG positivity in the blood donor controls was 2/500 (0.4%), significantly lower than that observed in the NHL patients (P < 0.0001). Both these blood donors were found to have CD. Only in one anti-h-tTG-positive NHL patient was there intestinal mucosa atrophy, and follow-up confirmed a CD diagnosis (CD frequency in NHL patients is 1.2%; versus blood donors: P = 0.4). In all the other seven anti-tTG-positive NHL patients a normal intestinal architecture was found, although, inflammatory infiltration of the lamina propria was observed in four patients. No anti-tTG-positive NHL patients, including the subject diagnosed as having CD, had a family history of CD, and all had normal weight and no signs of malabsorption. Anti-tTG false positive results were associated with a higher frequency of serum autoantibody positivity and T-cell type NHL. In conclusion, NHL patients the anti-tTG assay often gives discordant data with the EmA assay, with a high frequency of anti-tTG false positive results for CD diagnosis.     

The patient with slightly elevated pancreatic enzymes and abdominal complaints

Abdominal complaints in combination with slightly elevated serum pancreatic enzymes represent a classical clinical challenge. These symptoms may be due to coincidental unrelated harmless disorders, benign pancreatic alterations which are fairly easily treatable such as mild acute pancreatitis or uncomplicated chronic pancreatitis. However, serious, often insidious diseases such as pancreatic tumours may also present with this constellation as their first signs. Diagnostic procedures need to be stratified according to acuteness and severity of symptoms. While patients with acute onset of symptoms and severe complaints need immediate and combined laboratory and imaging investigations to allow adequate therapy, chronic and mild complaints usually justify a stepwise diagnostic approach consecutively using abdominal ultrasound, CT/MRI and endoscopic ultrasound as imaging procedures and reserving ERCP for cases which remain unclear or in which interventional therapy is needed. Diagnosis and follow-up are often particularly demanding in patients with cystic tumours of the pancreas. In chronic pancreatitis patients pain therapy and adequate control of pancreatic exocrine insufficiency may pose major problems. Patients with refractory pain may ultimately require surgical intervention. Another important indication for surgery in chronic pancreatitis is suspicion of cancer that cannot be ruled out by dedicated diagnostic procedures. This also applies to cystic tumours of the pancreas, which have a high risk of malignant transformation or may even already represent pancreatic cancer at the time of diagnosis.     

Adherence to gluten-free diet and serum antigliadin antibodies in celiac disease

In 134 patients with celiac disease the compliance with a gluten-free diet (GFD) and the presence of antigliadin antibodies (AGA) were evaluated. Compliance with the GFD was good in 71%, moderate in 11% and poor in 18%. High levels of AGA (IgA and IgG) were found in 24.2% of patients with good GFD, in 40% of those with moderate GFD and in 75% of those with poor GFD compliance. Our data suggest that the presence of AGA is correlated with the degree of adherence to the GFD, and that AGA measurement may be of some value in the monitoring of GFD in patients with celiac disease.     

Addison's disease as a rare cause of chronically elevated liver enzymes

Common causes of chronically elevated serum liver enzymes include fatty liver disease, chronic viral hepatitis, autoimmune hepatitis, or hereditary metabolic disorders. Adrenocortical insufficiency can also cause elevated liver enzymes. Since 1990 only 11 cases have been reported. We here report a 52-year-old man with elevated liver enzymes (1.5 x upper limit of normal) over the past 10 years. Furthermore, hyponatremia and hyperkalemia were noted. He complained of fatigue and low blood pressure over the past few years. At physical examination a dark complexion was noted. After ruling out chronic viral hepatitis, autoimmune disease, metabolic or hereditary disorders, rare causes of elevated liver enzymes were considered. The endocrinological work-up revealed Addison's disease as cause of serum electrolyte disturbance and elevated liver enzymes. The patient was successfully treated with hydrocortisol and fludrocortisol. After one week, liver enzymes, serum electrolytes and arterial blood pressure had normalized. In conclusion, for patients with constantly elevated liver enzymes also rare, extrahepatic diseases have to be considered. Addison's disease is a rare but fully reversible cause for elevated liver enzymes.     

Smoking and celiac disease: a population-based cohort study.

BACKGROUND & AIMS: Earlier studies indicate a protective effect of smoking against celiac disease (CD), but have been based on small numbers and retrospective collection of smoking data. METHODS: We linked the Swedish national inpatient register and the medical birth register to study the association between smoking status during pregnancy and CD (diagnosed or undiagnosed at delivery) in women who were pregnant from 1983 to 2001. We adjusted for civil status, age, and year when smoking data were collected. We identified 873 cases of CD (636 diagnosed and 237 undiagnosed). RESULTS: Of 249,967 smokers, 67 (.27%) had undiagnosed CD (vs 170 of 794,912 nonsmokers [.21%]) (odds ratio [OR], 1.25; 95% confidence interval [CI], .94-1.66; P = .118). Point estimates remained unchanged when adjusting for civil status, age, and year of smoking data collection (adjusted OR [AOR], 1.25; 95% CI AOR, .94-1.67). There were no associations between smoking and future (undiagnosed at delivery) CD when we adjusted for potential confounders and stratified for comorbidity or time to diagnosis (< 5 vs > or =5 y after infant birth). In women with diagnosed CD, smoking was more common than in women who never had a diagnosis of CD (AOR, 1.36; 95% CI AOR, 1.12-1.64; P = .002). CONCLUSIONS: Smoking seems to have little effect on the risk for future CD in pregnant women.     

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.     

Intestinal lysosomal enzymes in the diagnosis of pancreatic disease.

Acid hydrolases (lysosomal enzymes) were analyzed and compared with trypsin in duodenal juice obtained after a test meal (Lundh test). The possible diagnostic role of acid hydrolases in pancreatic disease was investigated. In all patients with chronic pancreatitis normal values of acid hydrolases but subnormal trypsin activities were found. In pancreatic cancer normal values of acid hydrolases and normal trypsin values were seen in three patients with small tumors, whereas five patients with more advanced cancer of the pancreas had decreased trypsin activity and three of them high activities of acid hydrolases in duodenal juice. In five patients operated on with a gastroenteroanastomosis acid hydrolases were markedly increased. Five patients had no activity of acid hydrolases in the aspirate, probably reflecting technical failure with dislodgement of the catheter from the duodenum to the stomach. In conclusion the assay of acid hydrolases does not seem to increase the diagnostic value of the conventional Lundh test (trypsin).     

Unexplained bronchopulmonary disease with inflammatory bowel disease.

Six patients developed severe, unexplained, chronic bronchopulmonary disease from 3 to 13 years after the onset of nonspecific inflammatory disease of the colon. All had chronic bronchitis, bronchiectasis was diagnosed in four, and an obstructive type of pulmonary dysfunction was noted in five. Four of the six, including the two with only chronic bronchitis, had no history of smoking. There was an initial correlation between the pulmonary symptoms and the intestinal disease, except in two patients who developed overt pulmonary disease following total proctocolectomy. The frequent occurence of extraintestinal lesions has suggested that ulcerative colitis and regional enteritis are systemic disorders. Chronic unexplained bronchopulmonary disease may be another infrequent complication in such patients.     

Behaviour of serum pancreatic enzymes in chronic pancreatitis

AIM: To establish whether serum pancreatic enzyme determination is useful in the identification of patients with chronic pancreatitis and in revealing the presence of exocrine pancreatic insufficiency PATIENTS AND METHODS: A total of 50 patients with chronic pancreatitis were included in the investigation: 19 were studied during a painful attack of the disease and 31 were observed during clinical remission of the disease and underwent a secretin-caerulein test; 21 of the 31 patients had severe pancreatic insufficiency. Thirty patients with non-pancreatic digestive diseases were also studied. Serum amylase, pancreatic isoamylase, lipase, trypsinogen and elastase- were determined in all patients. RESULTS: Serum levels of the 5 enzymes studied were significantly higher in patients with pancreatic pain than in those studied during a clinical remission of the disease, and in those with non-pancreatic digestive diseases. In patients with chronic pancreatitis studied during clinical remission of the disease serum levels of pancreatic isoamylase and trypsinogen were significantly lower than in those patients with non-pancreatic digestive diseases. Considering only low serum concentrations of the five enzymes studied in diagnosing chronic pancreatitis, trypsinogen showed a sensitivity of 28%, specificity of 100%, a predictive value of a positive test of 100% and a predictive value of a negative test of 96.4%. In the 21 patients with severe pancreatic insufficiency, abnormally low serum concentrations of trypsinogen were found in 12 patients (57%), of lipase and elastase-1 in 6 (29%), of pancreatic isoamylase in 5 (24%), and of amylase in 3 (14%). CONCLUSIONS: Serum pancreatic enzymes can not be considered a useful tool to identify patients with pancreatic insufficiency. However, of the five enzymes studied, serum trypsinogen appears to be a useful marker in the diagnostic work-up of chronic pancreatitis.