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Steatorrhea and weight loss in a 72-year-old man: primary biliary cirrhosis? Celiac disease? Bacterial overgrowth? What else?

Unintentional weight loss is an ominous sign, particularly when it occurs in the elderly; concern for malignancy is especially worrisome. In this report, we describe a 72-yr-old man who presented with weight loss and was found to have massive steatorrhea. An extensive evaluation revealed evidence of primary biliary cirrhosis (PBC), celiac disease, and small intestinal bacterial overgrowth. No malignancy was identified. The weight loss was attributed to severe steatorrhea due, in part, to intraluminal bile salt deficiency, small bowel mucosal disease, and bacterial overgrowth. Several points are discussed regarding gastrointestinal function in elderly patients with chronic liver disease secondary to PBC. The rare association between PBC and celiac disease in adults is also discussed. Finally, we suggest that bacterial overgrowth plays a significant role in the development of steatorrhea in some persons with PBC and that an assessment for bacterial overgrowth should be performed on persons with steatorrhea and PBC.

Aged↗

[A comparison between antigliadin antibodies and blood xylose in celiac disease].

We have compared serum antigliadin antibodies (AGA) with xylose absorption test in diagnosis and follow-up of pediatric celiac disease. Three groups of children were investigated: celiacs, affected by other gastrointestinal disease, healthy controls. On gluten diet AGA IgA, IgG and xylose test were abnormal in all celiac children. After only three months of gluten-free diet, abnormal AGA IgA values were found in 3%, AGA IgG in 63%, xylose test in 28% of children. Normal values for AGA IgA and IgG and for xylose test were found between 7 and 20 months. On challenge, after 1-4 months of gluten diet, abnormal AGA IgA and IgG values were found in 90% of cases, xylose test only in 27%. As far as the children with other gastrointestinal disease are concerned, 2% had abnormal values for AGA IgA, 22% for AGA IgG and 42% for xylose test. All healthy children had normal AGA IgA, IgG values and xylose test. Our date show AGA IgA the most specific laboratory test, among these investigated, for diagnosis and follow-up of celiac disease.

Adolescent↗

Untractable diarrhea due to late onset celiac disease of the adult following pancreatoduodenectomy.

This case describes a rare cause of severe diarrhea that may occasionally plague the postoperative course of pancreatic resections. Although exceedingly rare this complication has already been described in another two patients undergoing pancreatoduodenectomy with diagnosis of duodenojejunal adenocarcinoma. Surgeons dedicated to pancreatic resections as well as pancreatologists caring for these patients should retain this possibility in their cultural background. Diarrhea, due to either exocrine insufficiency or interruption of sympathetic nerves to the small intestine, is a common complaint after pancreatoduodenectomy. A 54-year-old white female after a pancreatoduodenectomy with standard lymphatic clearance developed intractable diarrhea leading to severe cachexia. Recognition of the underlying occult celiac disease and institution of the appropriate dietary regimen allowed quick and expeditious recovery.

Acute Disease↗

[Comparative characteristics of biliary lipids in celiac disease and chronic enteritis].

The lipid components of duodenal contents (DC) and of gallbladder bile (GB), i.e. bile acids, phospholipids, and neutral lipids, as well as the fatty-acid composition of common lipids in celiac disease and chronic enteritis (CEN) were found, in the course of this study, to be specific and to differ between themselves to a great extent. The determination of the ratio of indices for 16:0 and 18:1 fatty acids and level 20:4 of an acid in the composition of common lipids of DC and GB could be used as a criteria in the differential diagnosis of celiac disease and CEN.

Adult↗

Rhabdomyolysis in celiac disease.

A 12-year-old female presented with chronic diarrhea, fatigue, failure to thrive, sudden weakness of her upper and lower extremities and inability to walk. On neurological examination, atrophy was found of the lower extremity muscles, coupled with muscle weakness. Hypokalemia and a high creatine kinase (CK) level were detected. Antigliadin IgA, IgG and antiendomysial antibodies were positive. A duodenal biopsy revealed the classical findings of celiac disease. To our knowledge this is the first childhood case of celiac disease presenting with rhabdomyolysis.

Celiac Disease↗

Down's syndrome and celiac disease.

The association between Down's syndrome (DS) and autoimmune diseases has long been recognized. However, its relationship to celiac disease (CD) has only recently been reported, and a clear-cut association remains to be fully established. We have studied the prevalence of CD in a random sample of 70 individuals with DS. IgA anti-gliadin antibodies (IgA AGAs) were determined in all and found to be positive in nine (13%). In eight, anti-endomysium antibodies (AEAs) were investigated, and jejunal biopsies were performed. AEAs were positive in two, and three had flat intestinal mucosa. The class I and II human leukocyte antigens of two patients with CD were determined. Results were as follows: A2/B8 B39/DR1 DR3/DQW1 DQW2 in one case and A2 A28/B44 B17/DR4 DR5/DQW3 in the other. This implies a 43% prevalence of CD in DS, which is well above that previously found by us in our population (0.62/1,000 live births). We conclude that the association between DS and CD is not fortuitous and suggest that the determination of such serologic markers as IgA AGA and AEA should be part of health assessment in DS patients.

Adolescent↗

Magnifying endoscopy of the duodenum with dye scattering method in a case with celiac disease.

AIM: To know the more detailed findings of the small intestinal mucosa with the use of a magnifying endoscope and a vital dye, and the efficacy of the both tools. PATIENT AND METHODS: A 54-year old female patient with celiac disease. The duodenal mucosa downward as far as the descending portion was observed with a magnifying endoscope (Olympus GIF HM) before and after spraying the mucosa with 0.1% indigo carmine. RESULTS: The endoscopy clarified the atrophy and edema of each villus, and scattering of the dye revealed shorter villi with the relatively longer villi remaining in islands. CONCLUSION: The combination of magnifying endoscopy and the dye scattering method is useful for closer observation of the intestinal mucosa in celiac diseases.

Celiac Disease↗

Pica as a presenting symptom in childhood celiac disease.

Persistent pica may be either a cause or a result of iron deficiency. Three children are described with long-standing pica and iron-deficiency anemia and in whom total villous atrophy consistent with celiac disease was found on jejunal biopsy. Additional findings included short stature, delayed bone age, and impaired xylose absorption. A dramatic growth spurt and complete resolution of pica were observed after a gluten-free diet. In these cases pica evidently resulted from iron deficiency secondary to malabsorption. Underlying celiac disease should be considered in children with persistent pica and growth failure even if gastrointestinal disturbances are minimal.

Anemia, Hypochromic↗

Cirrhosis in children with celiac disease.

BACKGROUND: Liver involvement represents an extra-intestinal feature of celiac disease (CD) and shows a clinical spectrum varying from nonspecific reactive hepatitis to cirrhosis. Here we report the association of cirrhosis with CD in 5 children. PATIENTS AND METHODS: The mean age of the patients was 9.4 +/- 2.8 years. Viral, metabolic, and autoimmune etiology of liver disease was ruled out. Intestinal and liver biopsies were performed to confirm the histologic diagnosis in all subjects. RESULTS: Three of the patients had chronic diarrhea and hepatosplenomegaly in whom diagnoses of CD and cirrhosis were established at presentation simultaneously. In the other 2 patients, CD was diagnosed following an initial diagnosis of cirrhosis. At diagnosis, alanine aminotransferase (range, 64-271 IU/L) and aspartate aminotransferase (range, 90-225 IU/L) values were elevated. After 1 to 5 years of a gluten-free diet (GFD), normalization of serum aminotransferase levels and clinical improvement were observed in 3 patients with strict GFD. The other 2 patients without improvement of the liver disease had poor dietary compliance. CONCLUSION: CD may be associated with severe hepatic damage in children and strict GFD may have beneficial effect on the course of liver disease. Serologic screening of CD should be included in differential diagnosis of chronic liver disease of unknown origin.

Adolescent↗

A new morphological classification during follow-up in patients with celiac disease: a three-dimensional observation by scanning electron microscopy.

The structure and ultrastructure of the villi of small intestinal mucosa was examined in 237 duodenal or jejunal biopsies taken from children with active celiac disease and during gluten-free diet. All biopsies were processed for light and scanning electron microscopy. Conventional histology showed four different morphological aspects: total and subtotal villous atrophy in patients on unrestricted diet, partial villous atrophy and normal mucosa during gluten-free diet. Scanning electron microscopy demonstrated that in active celiac disease the severity of the intestinal lesions was related to individual vulnerability to gluten. Our results showed that during dietary treatment the process of mucosal healing was constant and strictly time-dependent. Furthermore, the ultrastructural examination has been relevant in evaluating the evolution of the villous regeneration. In this study a classification regarding the healing process of the small intestinal mucosa correlated with the time of start of dietary therapy is proposed.

Adolescent↗

[Dermatitis herpetiformis occuring in patients with celiac disease in childhood].

BACKGROUND: Dermatitis herpetiformis (DH) is a chronic papulovesicular immune-mediated disorder associated with gluten-sensitive enteropathy. We report eight cases in which DH appeared many years after celiac disease (CD) in child. PATIENTS AND METHODS: The diagnosis of CD was based on histological features of total or subtotal villous atrophy, full remission after withdrawal of gluten from the diet, and eventually circulating antibodies (IgA gliadin, antireticulin and antiendomysium) at the time of diagnosis and their disappearance under gluten-free diet. The diagnosis of DH was made from clinical findings, histological examination of the involved skin and direct immunofluorescence microscopy of normal or perilesional skin. HLA class II typing was performed in five patients. DRB1, DQA1, DQB1 and DBP1 alleles were studied. RESULTS: DH appeared between 3 and 22 years after the initial diagnosis of CD. Five patients did not show at that time any digestive symptoms. In three cases, a break in the gluten-free diet or a recent revival of the normal diet preceded the rash. In only one case, DH appeared while the patient was under gluten-free diet. In three patients, the rash appeared many years after the gluten-free diet had been stopped. Phenotype DR3 and/or DR7 of the celiac disease could be found in four of the five patients studied; three of them were found to bear DQW2. The DR2 allele was not found in any of the five tested patients. DISCUSSION: These eight cases illustrate the absence of precise nosological barrier between gluten-sensitive enteropathy of the DH and that observed in CD. The presence of the DR7 allele, and especially the absence of the DR2 allele, could explain the particularly severe and symptomatic course of the enteropathy in these patients. The delay in the appearance of DH, after a very variable period of normal diet, could correspond to the necessary time for progressive accumulation of IgA (or immune complex IgA-gluten) in the skin after a digestive sensitization to gluten. The preventive role of gluten-free diet is thus probable. CONCLUSION: CD and DH likely correspond to two different stages of the same disease, thus requiring a prolonged follow-up of both digestive and skin tissues. Long-term eviction of gluten to prevent eventual DH must be balanced with the demand and the cost of such a diet.

Celiac Disease↗

[Recurrent tetany as the first symptom of late manifesting celiac disease].

BACKGROUND: The diagnostic classification of a malabsorption is often made more difficult, particularly in oligosymptomatic forms. CASE REPORT: A female patient is presented, where the diagnosis of malabsorption syndrome was concluded because of recurring tetanias. This could be traced back to an oligosymptomatic celiac disease. Diagnostic course of action, differential diagnosis as well as further observation during therapy are discussed. CONCLUSION: Oligosymptomatic developments of celiac disease are common amongst adults and present a diagnostic challenge. The existence of a malabsorption should be considered, even if the momentary individual symptoms are unclarified.

Adult↗

Iron deficiency in children with celiac disease.

To evaluate the incidence of either evident anemia or a subclinical status of iron deficiency in celiac disease (CD), we studied 80 celiac children aged 6 months to 18 years. They were subdivided into various groups according to morphology of gut mucosa and diet. Only eight of 47 celiac children had an evident anemia at the time of the first peroral bowel biopsy. In addition, 51% of the patients with atrophic mucosa and 56% of the children on a gluten-containing diet had serum iron levels less than 50 micrograms/dl; 35% of patients of both groups had serum ferritin levels less than 12 micrograms/L. On the contrary, only a small number of children with normal mucosa on a gluten-free diet showed a laboratory, subclinical picture of iron deficiency. The results of our study can therefore be summarized in three major items: (a) Low levels of both serum iron and ferritin can frequently be found during active CD. (b) Regular determination of serum iron levels appears to be useful in controlling the state of iron stores in such patients, as well as in deciding whether and when to recommend temporary iron supplementation. (c) Serum ferritin tests did not offer more information than the easier and cheaper serum iron determinations.

Adolescent↗

Dermatitis herpetiformis and celiac disease are both primarily associated with the HLA-DQ (alpha 1*0501, beta 1*02) or the HLA-DQ (alpha 1*03, beta 1*0302) heterodimers.

HLA-DRB1,-DQA1, and -DQB1 genomic typing of 50 patients with dermatitis herpetiformis and of 290 healthy blood donors was performed. Genes encoding the DQ (alpha 1*0501, beta 1*02) heterodimer were carried by 43 (86%) of the patients and 72 (25%) of the controls. Of the remaining seven patients six (12% of all the patients) carried genes encoding the DQ (alpha 1*03, beta 1*0302) heterodimer. These HLA associations are very similar to those observed in patients with celiac disease. We thus conclude that dermatitis herpetiformis and celiac disease are associated to the very same HLA-DQ alpha beta heterodimers.

Case-Control Studies↗

Dermatitis herpetiformis and gluten sensitive enteropathy (including celiac disease)--increased subepithelial extracellular matrix viscosity due to gliadin.

It is now firmly established that dermatitis herpetiformis (DH) is associated with gluten sensitive enteropathy (GSE), although the GSE of DH is generally milder than that form which occurs in celiac disease. The toxic fraction of gluten is in the gliadin, a protein fraction. Gliadin is absorbed in GSE and antigliadin antibodies are present in both DH and celiac disease. There is a question of a cross reactivity between reticulin and gliadin. Gliadin is reported to bind to reticulin. Reticulin has a glycosaminoglycan component. Fibronectin, another component of ground substance, also binds to reticulin. Reticulin and fibronectin are important in basement membrane areas and play a role in basement membrane attachment. Gluten may also exert a lectin effect on gastrointestinal mucosa which contributes to the underlying extracellular matrix. DH and GSE have different pathologies because of their different anatomical sites. The pathomechanisms of both diseases can be explained by one mechanism. Gliadin, or a peptide fraction from it, enters or combines with the extracellular matrix and increases tissue viscosity. The protein fraction of glycosaminoglycans in the extracellular matrix is known to control viscosity. In DH the increased extracellular matrix viscosity would interfere with the diffusion of tissue fluid in the dermal papillae and leads to vesicle formation. The intestinal villi serve a very different function. In GSE the increased extracellular matrix viscosity would decrease adsorption from the intestinal tract producing villi with less volume (shortened or atrophic). The shortened villi decrease the production of digestive enzymes and the absorptive surface. The decreased movement of nutrient tissue fluid supplied to the intestinal epithelial cells also eliminates the microvilli.(ABSTRACT TRUNCATED AT 250 WORDS)

Celiac Disease↗

Association of celiac disease with microsatellite polymorphisms close to the tumor necrosis factor genes.

Celiac disease is tightly linked to the MHC class II region on chromosome 6. We have studied two highly polymorphic microsatellite loci, TNFa and b, near the TNF genes in the class III region of the MHC, for evidence of their association to CD, as compared to a control population. Our findings show that the microsatellite allele most significantly associated with the disease is TNFb3, which is found in 86.3% of CD patients versus 24.5% of controls, with allele frequencies of 0.5392 and 0.1290, respectively (p < 0.001). The TNFa2 allele had a frequency of 0.6122 in CD patients and 0.2627 in controls (p < 0.001), with phenotype frequencies of 87.8% and 50.0%, respectively. TNFa6 and -a11 and TNFb5 have significantly reduced frequencies in CD patients. TNFb3 shows a maximal level of linkage disequilibrium with HLA-DQB1*0201 in celiac patients. However, while the DQB1*0201/TNFa2 haplotype was strongly associated with CD, DQB1*0201 was not significantly in linkage disequilibrium with TNFa2, suggesting that TNFa2 is independently associated with CD. This association could have functional significance as TNFa2 has been correlated with high TNF production.

Celiac Disease↗

Increased levels of circulating ICAM-1, E-selectin, and IL-2 receptors in celiac disease.

Adhesive interactions between endothelium and circulating cells are crucial for the development of inflammatory reactions. We found significantly higher serum levels of soluble intracellular adhesion molecule-1 (sICAM-1, 492.5 +/- 22.1 ng/ml) in patients with active celiac disease (including IgA-deficient patients) than in patients on a gluten-free diet (335.7 +/- 20.0 ng/ml) (P < 0.001) and healthy controls (207.4 +/- 11.2 ng/ml) (P < 0.001). The concentration of soluble E-selectin in sera from celiac patients (37.2 +/- 3.4 ng/ml) was also higher (P < 0.001) than in sera from healthy controls (15.5 +/- 0.7 ng/ml) but, in contrast to sICAM-1, it remained high in the patients after treatment (30.2 +/- 2.7 ng/ml). Interestingly, the concentration of circulating soluble interleukin-2 receptors, molecules indicating lymphocyte activation, was only increased in sera from patients with active celiac disease (2943.0 +/- 214.1 pg/ml), and the level in sera from treated patients and healthy controls was comparable (1936 +/- 349 and 1416 +/- 111.7 pg/ml). The elevated serum level of soluble cell adhesion molecules could be used as a supplementary, noninvasive procedure for monitoring intestinal immune reactions.

Adolescent↗

Specific reactivity of fluorescein isothiocyanate-conjugated separated IgG and IgA from celiac disease sera on human tissues.

Study of the reaction of celiac disease-related antibodies with human substrates has been hampered by the immunological cross-reactivity between fluorescein isothiocyanate-conjugated anti-human immunoglobulins and immunoglobulins normally present in human tissues. In order to overcome this problem we extracted IgG from 2 celiac disease sera (positive for specific IgG and IgA antibodies) using a genetically engineered recombinant form of streptococcal protein G covalently immobilized on 4% agarose beads. The separated IgG and IgA was conjugated with fluorescein isothiocyanate and used in direct immunofluorescence on 0 blood group human duodenum, liver, and myocardium. Staining of the lamina propria beneath the villous epithelium, the endomysium of smooth muscle layers in the duodenum, and the liver sinusoidal and pericellular myocardial matrix was observed. The reactivity of celiac disease-related antibodies with various human tissues indicates that these antibodies are the result of a systemic immune response directed against all tissues containing matrix proteins.

Animals↗