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Weekly Clinicopathological Exercises F O U N D E D B Y R I C H A R D C . C A B O T

R OBERT E. S CULLY

, M.D.,

Editor

E

UGENE

J. M

ARK

, M.D.,

Associate Editor

W

I LLI A M

F. M

C

N

EELY

, M.D.,

Associate Editor

J

O

-A

NN E

O. S

H EPA R D

,

M.D., Associate Editor

S

ALLY

H. E

BELING

, Assistant Editor

S

TA C EY

M. E

LLENDER

,

Assistant Editor

C

H R I S TI N E

C. P

ETER S

, Editorial Staff

Case Records of the Massachusetts General Hospital

276

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N Engl J Med, Vol. 345, No. 4

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The New England Journal of Medicine

Case 23-2001

PRESENTATION OF CASE

An 18-month-old girl was admitted to the hospi-tal because of diarrhea with intermittent constipationand vomiting.

The child had been born by cesarean section, per-formed because of a breech presentation, at 41 weeks’gestation; it was the mother’s first pregnancy. Thechild’s immunizations were up to date. She had hadotitis media at 13 months of age. She was fed cow’smilk–protein formula and grew normally, withoutdiarrhea. At 15 months, her weight was 9.8 kg (30thpercentile). Her only medication was a fluoride sup-plement.

Six weeks before admission, the child became irri-table, and diarrhea developed, with foul-smelling, wa-tery stools but no fever or vomiting. Her pediatri-cian recommended a diet without dairy products,

vegetables, or fruit.Projectile vomiting developed four days later and

continued for nine days. Four weeks before admission,the child’s weight was 8.75 kg (below the 5th per-centile). Laboratory studies were performed (Table 1).

An abdominal radiograph showed a moderate amountof gas in the stomach and dilated loops of small in-testine. Subsequently, she had an episode of “explo-sive” diarrhea, followed by a four-day period withoutbowel movements or vomiting. The diarrhea then re-curred. Nine days before admission, the child wasevaluated elsewhere. A stool culture was negative. Noparasites or ova were detected, and tests for rotavirusand for Clostridium difficile

toxin were negative. A gluten-free diet started six days before admissionresulted in improvement in the diarrhea.

Four days before admission, the girl was brought tothis hospital. Physical examination revealed a distend-ed, tympanitic abdomen. Rectal examination showed

firm stool; a test for occult blood was negative. Anabdominal ultrasonographic study showed distentionof the gallbladder, with sludge. An upper gastrointes-tinal series with a small-bowel follow-through study (Fig. 1) showed diffuse dilatation of the small bowel

with fluid and contrast material; there were no mu-cosal abnormalities or filling defects. During the twodays before admission, the child took smaller feed-

*To convert the value for creatinine to micromoles per li-ter, multiply by 88.4.

T

ABLE

1.

B

LOOD

C

HEMICAL

V

ALUES

.

V

ARIABLE

F

OUR

W

EEKS

BEFORE

A

DMISSION

O

N

A

DMISSION

Urea nitrogen Normal NormalCreatinine (mg/dl)* 0.2 NormalGlucose Normal NormalSodium (mmol/liter) 137 137Potassium (mmol/liter) 4.5 3.6Chloride (mmol/liter) 107 105Carbon dioxide (mmol/liter) 17 17.6

Anion gap (mmol/liter) 18

Figure 1.

Image from a Small-Bowel Follow-through Study,Showing Dilated Proximal Loops of Small Bowel ContainingFluid and Contrast Material.

Copyright © 2001 Massachusetts Medical Society. All rights reserved.Downloaded from www.nejm.org by CRUZ EDGAR MD on January 13, 2009 .



CASE RECORDS OF THE MASSACHUSETTS GENERAL HOSPITAL


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277

ings, continued to have diarrhea with occasional vom-iting, and became listless, with minimal urinary out-put. She was urgently admitted to the hospital.

The child’s temperature in recent days had not ex-ceeded 37.7°C. She had received no antibiotics duringthe preceding two months. Her paternal great-grand-mother and a paternal cousin had Crohn’s disease, amaternal uncle had lactose intolerance, and her mater-nal grandmother had a hiatal hernia and gastroesoph-ageal reflux disease. Her mother had thyroid diseaseand unexplained anemia, and her father had asthma.There was no family history of celiac disease or cys-tic fibrosis.

The rectal temperature was 36.9°C, the pulse was128, and the respirations were 28. The blood pressure

was 95/55 mm Hg. The weight was 8.82 kg (below the 5th percentile), and the length was 77 cm (25thpercentile).

On examination, the child appeared tired and irri-table. She was thin, with wasted thighs and buttocks.There was considerable abdominal distention, withactive bowel sounds.

Laboratory tests were performed (Tables 1 and 2),followed by a diagnostic procedure.

DIFFERENTIAL DIAGNOSIS

D

R

. C

HRISTOPHER

P. D

UGGAN

*: May we review the radiographic studies?

D

R

. S

UDHA

A. A

NUPINDI

(Pediatric Radiology): An image from the small-bowel follow-through study performed four days before admission (Fig. 1) showsmultiple dilated proximal small-bowel loops contain-ing contrast material and fluid, and the overall ap-pearance suggests a malabsorptive process. The pre-dominance of proximal small-bowel involvement isconsistent with the presence of celiac disease.

D

R

. D

UGGAN

: Although acute diarrhea is one of the most common symptoms of infection in infantsand young children, this child had persistent diarrhea(defined by the World Health Organization as diar-rhea of more than 14 days’ duration).

1

The associationof the diarrhea with malnutrition narrows the differ-ential diagnosis. The chief causes of diarrhea and mal-nutrition in children of this patient’s age are shownin Table 3.

Iatrogenic Malnutrition

Although the term iatrogenic malnutrition seems judgmental, physicians often suggest empirical andrestrictive dietary changes when treating children withdiarrhea, as in the case under discussion. When ano-rexia due to an infection is pronounced, the reductionof food intake can have important nutritional conse-quences.

2

In 1948, Chung and Vi≤∫orová

3

showedthat continued feeding during an episode of acute di-arrhea did not prolong the illness. Randomized trialsby Santosham et al.

4

and Brown et al.

5

in the 1980s

demonstrated that nutritional status could be pre-served and the duration of illness reduced when full-strength (vs. dilute) formulas were provided to children

with acute diarrhea. The current recommendationof the American Academy of Pediatrics for treatingacute diarrhea is to avoid a highly restrictive diet andinstead offer a wide variety of foods, including freshfruits, vegetables, lean meats, and breast milk or full-strength, lactose-containing formulas when appropri-ate.

6,7

This child had persistent diarrhea in the absenceof an unusually restrictive diet; prolonged withhold-ing of food is therefore unlikely to be the sole causeof the malnutrition.

T

ABLE

2.

H

EMATOLOGIC

L

ABORATORY

V

ALUES

ON

A

DMISSION

.

V

ARIABLE

V

ALUE

Hematocrit (%) 37.6Erythrocyte sedimentation rate

(mm/hr)2

White-cell count (per mm

3

) 5,600Differential count (%)

NeutrophilsLymphocytes

Atypical lymphocytesMonocytes

2570

14

Platelet count (per mm

3

) 279,000

*Director, Clinical Nutrition Service, Division of Gastroenterology andNutrition, Children’s Hospital; assistant professor of nutrition, HarvardSchool of Public Health; assistant professor of pediatrics, Harvard MedicalSchool — all in Boston.

T

ABLE

3.

D

IFFERENTIAL

D

IAGNOSIS

OF

D

IARRHEA

AND

M

ALNUTRITION

IN

Y

OUNG

C

HILDREN

.

Restrictive dietTransport defect (e.g., glucose–galactose

malabsorption) Anatomical defect (e.g., intestinal atresia, or

gastroschisis)Chronic or severe hepatobiliary diseaseExocrine pancreatic insufficiency Cystic fibrosis

Giardia lamblia

infestationCryptosporidium infestation

Escherichia coli

infectionImmunodeficiency syndromeCrohn’s diseaseEosinophilic gastroenteropathy

Autoimmune enteropathy




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Congenital Disorders

The two large classes of diagnoses that remain tobe considered are malabsorption and maldigestion.Several congenital disorders of the gastrointestinaltract seem unlikely in this case because of the onsetof symptoms at 18 months of age. Chronic or severehepatobiliary disease also seems unlikely, since no signsor symptoms of hepatic disease are noted.

This child’s presentation is consistent with the di-agnosis of cystic fibrosis, the most common cause of inherited exocrine pancreatic insufficiency, and dis-tention of the gallbladder with sludge is consistent

with the diagnosis of hepatobiliary disease associated with cystic fibrosis. No mention is made of the pan-creas in the description of the ultrasonographic find-ings, but it may have been obscured by overlyingbowel gas. Even though in North America, cystic fi-brosis is diagnosed at a median age of 6 months andthis child is 18 months old,

8

it should be ruled out with a sweat test.

Infection with Giardia lamblia

Other, more likely causes of the clinical findingsin this case are diseases of the upper gastrointestinaltract mucosa. The occurrence of watery, profuse diar-rhea, the radiographic evidence of fluid-filled bowelloops, and the absence of blood in the stool pointto an enteropathy rather than a colitis. Infection of thesmall intestine with Giardia lamblia

or other para-sites can present with these findings. Giardia, a pro-tozoal parasite of the upper small bowel, often in-fects infants and young children, who may have nosymptoms, acute diarrhea that is self-limited, or chron-

ic diarrhea with malabsorption and weight loss. Al-though in this case a stool specimen was tested forova and parasites, examination of a single stool spec-imen has limited sensitivity for the diagnosis of par-asitic infections; at least three specimens must be ex-amined for optimal sensitivity.

Infection with Cryptosporidium

Other protozoa that infect the upper gastrointes-tinal tract include cryptosporidium species, cyclospo-ra species, Isospora belli,

and microspora species. Al-though the ability of these spore-forming organisms tocause acute or chronic diarrhea became apparent withthe epidemic of the acquired immunodeficiency syn-drome (AIDS), they can also cause gastrointestinal dis-ease in immunocompetent persons.

9

One water-borneoutbreak of cryptosporidiosis in Milwaukee involvedmore than 400,000 people.

10

These spore-formingprotozoal pathogens are endemic in children livingin tropical countries or in areas with poor sanitation.The infection may be asymptomatic or may cause a

wide range of symptoms, including severe, persistentdiarrhea. The organisms are intracellular, and althoughstool cultures are usually diagnostic, biopsy of the

small intestine may be required to establish the di-agnosis.

Infection with Escherichia coli

Bacteria that cause chronic diarrhea and malnutri-tion include enteropathogenic Escherichia coli

and themore recently recognized species, enteroaggregative

E. coli.

Infections with enteropathogenic E. coli

of-ten cause persistent diarrhea in children in develop-ing countries.

11

In addition, enteroaggregative E. coli

has been isolated from stool specimens obtained fromchildren under the age of five years in developingcountries, as well as in patients with AIDS and over-seas travelers. Marked slowing of growth may follow infection with enteroaggregative E. coli,

even if it issubclinical.

12

Since this child had not lived in a coun-try where symptomatic infections with these speciesof E. coli

are common, her symptoms were probably not due to them.

Other causes of intestinal diseases associated withmalabsorption include immunodeficiency syndromes(but this child had no history of recurrent infections),Crohn’s disease (but her erythrocyte sedimentationrate was normal and Crohn’s disease is unlikely to de-

velop at her age), eosinophilic gastroenteropathy andother allergic disorders (but she has no history of atop-ic symptoms), and celiac disease.

Celiac Disease

Patients with celiac disease have inflammation of the proximal small intestine associated with a lifelongintolerance to the wheat protein gluten. In children,the disorder is often manifested as persistent diar-rhea, malabsorption, malnutrition, and irritability —all of which were present in this case. Other, lesscommon clinical findings include constipation (withhypotonia and abdominal distention), short stature,dermatitis herpetiformis, dental hypoplasia, and vi-tamin or mineral deficiencies, including deficienciesof folate,

13

vitamin D,

14

and iron.

15

Celiac disease results from a combination of factors:a genetic predisposition, dietary exposure to wheatproteins, and immunologic mechanisms, which arebecoming better understood. The disease is closely linked with HLA phenotypes B8, DR3, and DQw2,and the prevalence of celiac disease is very high amongpatients with autoimmune disorders — for example,autoimmune thyroid disease, insulin-dependent dia-betes mellitus, and Sjögren’s syndrome. One of theunique epidemiologic features of celiac disease is itshigh prevalence in areas where wheat is a staple of the diet. In western Ireland, for example, the preva-lence of the disease has been reported to be as highas 1 case per 300 newborn infants.

The antiendomysial IgA antibody is a sensitiveand specific serologic marker for celiac disease thathas been widely used,

16

although patients with an IgA deficiency may have false negative results. The use of






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blood tests to screen for celiac disease has greatly altered our conception of the illness, since popula-tion-based studies have shown a surprisingly highprevalence of silent celiac disease. In one study, theprevalence of asymptomatic celiac disease was 5 cas-es per 1000 children.

17

In a recent study of blooddonors in the United States, the prevalence of posi-tive tests for antiendomysial antibodies was 1 case per250 donors.

18

Serologic screening of 1200 childrenat high risk for the disease (children with a variety of symptoms who were seen in pediatric gastroenterolo-gy or endocrinology clinics), followed by small-bowelbiopsy if the serologic test was positive, yielded a prev-alence of 1 case per 57 children.

19

Latent celiac diseasehas been reported in children with no abnormalitieson small-bowel biopsy performed while they were ona gluten-containing diet, but in whom clinical andbiopsy features of celiac disease subsequently devel-oped.

20

The antiendomysial-antibody test, an indirect fluo-rescence antibody test in which monkey esophagealtissue is used as a substrate, is expensive and laborious.Tissue transglutaminase is the antigen against whichantiendomysial antibody is directed,

21

and some stud-ies have reported that antibody tests for this enzymehave high sensitivity and specificity.

22,23

I suspect that this patient underwent a small-bow-el biopsy, which remains the gold standard for thediagnosis of celiac disease. I wonder whether thechild’s mother, who was said to have thyroid diseaseand anemia of unclear cause, also had celiac disease.

D

R . R. A LAN B. E ZEKOWITZ (Pediatrics): It usedto be said that one of the clinical signs of celiac dis-ease is wasting of the medial portions of the buttocks.Is it still regarded as a clinical hallmark of the dis-ease, and if so, why does it occur selectively in pa-tients with celiac disease?

D R . D UGGAN : Such wasting is a characteristicfinding, but I have seen a number of malnourishedchildren without celiac disease who have had it.

CLINICAL DIAGNOSIS

Celiac disease.

DR. CHRISTOPHER P. DUGGAN’S

DIAGNOSIS

Celiac disease.

PATHOLOGICAL DISCUSSION

D R . J OSEPH M ISDRAJI : Examination of specimensfrom a biopsy of the small intestine showed completeloss of normal villous architecture, with mucosal flat-tening — so-called villous atrophy (Fig. 2). The laminapropria contained a dense lymphoplasmacytic infil-trate, and there was a prominent increase in intraep-ithelial lymphocytes (Fig. 3). These findings are con-sistent with, but not specific for, the diagnosis of celiac disease.

Biopsy specimens of the gastric antrum revealed adiffuse mononuclear-cell infiltrate in the lamina pro-pria and an increase in intraepithelial lymphocytes —findings consistent with the presence of lymphocyticgastritis (Fig. 4 and 5). Thiazine staining for Helico- bacter pylori was negative. Since lymphocytic gastritishas been reported in up to 45 percent of patients withceliac disease,24 its presence supports the diagnosis.Similarly, colonic-biopsy specimens from patients withceliac disease may reveal lymphocytic colitis.

Diseases other than celiac disease may cause sim-ilar changes in the small intestine. In adults, the main

Figure 2. Duodenal Specimen Showing Total Villous Atrophyand Crypt Hyperplasia — Findings Consistent with the Pres-ence of Celiac Disease (Hematoxylin and Eosin, ¬130).

Figure 3. Marked Increase in Intraepithelial Lymphocytes (Ar-rows) in Duodenal Surface Epithelium (Hematoxylin and Eosin,¬250).Numerous plasma cells are present in the lamina propria (ar-rowheads).




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disease in the differential diagnosis is peptic duoden-itis, which in severe cases may result in total villousatrophy. Except in patients with the Zollinger–Elli-son syndrome, however, the inflammation is usually confined to the first portion of the duodenum. 25 Itis therefore critical to determine the exact locationin the duodenum from which the specimen was tak-en, and it is advisable to obtain specimens from themore distal portions of the duodenum when clinicalfindings suggest the possibility of celiac disease.

Other conditions that may mimic celiac disease withrespect to the pathological findings include tropicalsprue, intestinal bacterial overgrowth, viral gastroen-teritis, giardiasis, Crohn’s disease, and lymphoma of the small intestine. 24,26 Consideration of these otherdiagnoses is particularly important when the biopsy specimen shows villous blunting rather than com-plete atrophy.

In children younger than two years of age, autoim-mune enteropathy, microvillous inclusion disease, andallergy to soy or cow’s milk or, in rare cases, otherfoods 24,27 must be added to the list of possible diag-noses.

Because the results of a biopsy of the small intes-tine are not specific for the diagnosis of celiac disease,confirmation of the diagnosis depends on the pres-ence of characteristic changes in the small intestineand unequivocal clinical improvement with a gluten-free diet. The presence of circulating IgA antireticu-lin and IgA antiendomysial antibodies supports thediagnosis. A gluten challenge is no longer consid-ered essential to establish the diagnosis.

D R . E UGENE J. M ARK (Pathology): Dr. Misdraji,are the lymphocytes B cells or T cells, and is subtyp-ing useful in making the diagnosis?

D R . M ISDRAJI : The intraepithelial lymphocytesare of T-cell lineage — specifically, g / d T cells. Sub-typing has no diagnostic utility.

D R . M ARK : Dr. Winter, will you tell us about theclinical follow-up on the patient?

D R . H ARLAND S. W INTER (Pediatrics): Two monthsafter the institution of a gluten-free diet, her symp-toms had completely resolved and her weight hadincreased from 9.0 to 10.3 kg (25th percentile).

D R . E ZEKOWITZ : Is this child at increased risk forinflammatory bowel disease, a malignant tumor, orautoimmune disease?

D R . W INTER : There is a small likelihood of thedevelopment of inflammatory bowel disease — eitherCrohn’s disease or ulcerative colitis.

D R . R ONALD E. K LEINMAN (Pediatrics): The in-cidence of autoimmune disease rises with increasingexposure to gluten. Among patients who are over theage of 10 years when celiac disease is diagnosed, theprevalence of autoimmune disease, including type 1diabetes mellitus, Graves’ disease, and Hashimoto’sthyroiditis, is 20 to 25 percent. Among patients in

whom the diagnosis is made before the age of two years, the prevalence of autoimmune disease is lessthan 5 percent. Patients with celiac disease are alsoat increased risk for malignant lymphoma and carci-nomas of the gastrointestinal tract. It has been sug-gested that the risk of these cancers is decreased if patients adhere to a strict gluten-free diet. 28 Many af-fected persons have minimal symptoms or none buthave antiendomysial antibodies in serum specimensand a slight increase in CD8+ intraepithelial lympho-cytes in specimens from small-bowel biopsy; these cellsincrease in number in successive biopsy specimens ob-tained over a period of several years.

D R . E ZEKOWITZ : This patient’s mother had thy-roid disease and anemia, raising the question of au-toimmunity. She may have excluded gluten from herdiet without realizing that it is associated with symp-toms of celiac disease.

D R . K LEINMAN : Often, one parent — and occa-

Figure 4. Antral Specimen with Diffuse Mononuclear Infiltratein the Lamina Propria (Hematoxylin and Eosin, ¬79).

Figure 5. Marked Increase in Surface Intraepithelial Lympho-cytes in Antral Mucosa (Arrow) — a Finding Consistent with the

Presence of Lymphocytic Gastritis (Hematoxylin and Eosin,¬250).





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sionally both parents — of a child with celiac diseasehas had long-standing, intermittent diarrhea that in-tensifies when a moderate amount of food contain-ing wheat is eaten. Also, in children with diabetes thatis difficult to manage, concomitant celiac disease issometimes the reason for the difficulty.

ANATOMICAL DIAGNOSIS

Celiac disease.

REFERENCES

1. Division of Diarrhoeal and Acute Respiratory Disease Control. Thetreatment of diarrhoea: a manual for physicians and other senior health

workers. Geneva: World Health Organization, 1995:1-54. (WHO/CDR/95.3.)2. Baker SS, Davis AM. Hypocaloric oral therapy during an episode of di-arrhea and vomiting can lead to severe malnutrition. J Pediatr Gastroen-terol Nutr 1998;27:1-5.3. Chung AW, Vi≤∫orová B. The effect of early oral feeding versus early oral starvation on the course of infantile diarrhea. J Pediatr 1948;33:14-22.4. Santosham M, Foster S, Reid R, et al. Role of soy-based, lactose-freeformula during treatment of acute diarrhea. Pediatrics 1985;76:292-8.5. Brown KH, Gastañaduy AS, Saavedra JM, et al. Effect of continued oralfeeding on clinical and nutrit ional outcomes of acute diarrhea in children.J Pediatr 1988;112:191-200.6. Provisional Committee on Quality Improvement, Subcommittee on

Acute Gastroenteritis. The management of acute gastroenteritis in youngchildren. Pediatrics 1996;97:424-35.7. Duggan C, Nurko S. “Feeding the gut”: the scientific basis for contin-ued enteral nutrit ion during acute diarrhea. J Pediatr 1997;131:801-8.8. Lai HC, Corey M, FitzSimmons S, Kosorok MR, Farrell PM. Compar-ison of growth status of patients with cystic fibrosis between the UnitedStates and Canada. Am J Clin Nutr 1999;69:531-8.9. Goodgame R. Understanding intestinal spore-forming protozoa: cryp-tosporidia, microsporidia, isospora, and cyclospora. Ann Intern Med 1996;124:429-41.10. MacKenzie W, Hoxie N, Proctor M, et al. A massive outbreak in Milwau-kee of cryptosporidium infection transmitted through the public water supply.N Engl J Med 1994;331:161-7. [Erratum, N Engl J Med 1994;331:1035.]11. Bardhan PK, Albert MJ, Alam NH, Faruque SM, Neogi PK, Ma-halanabis D. Small bowel and fecal microbiology in children suffering frompersistent diarrhea in Bangladesh. J Pediatr Gastroenterol Nutr 1998;26:9-15.

12. Poskitt EM, Cole TJ, Whitehead RG. Less diarrhoea but no change ingrowth: 15 years’ data from three Gambian villages. Arch Dis Chi ld 1999;80:115-20.13. Pittschieler K. Neutropenia, granulocytic hypersegmentation and coe-liac disease. Acta Paediatr 1995;84:705-6.14. Keaveny AP, Freaney R, McKenna MJ, Masterson J, O’Donoghue DP.Bone remodeling indices and secondary hyperparathyroidism in celiac dis-ease. Am J Gastroenterol 1996;91:1226-31.

15. Ackerman Z, Eliakim R, Stalnikowicz R, Rachmilewitz D. Role of small bowel biopsy in the endoscopic evaluation of adults with iron defi-ciency anemia. Am J Gastroenterol 1996;91:2099-102.16. Burgin-Wolff A, Gaze H, Hadziselimovic F, et al. Antigliadin and an-tiendomysium antibody determination for coeliac disease. Arch Dis Child1991;66:941-7.17. Catassi C, Ratsch IM, Fabiani E, et al. High prevalence of undiag-nosed coeliac disease in 5280 Italian students screened by antigliadin anti-bodies. Acta Paediatr 1995;84:672-6.18. Not T, Horvath K, Hill ID, et al. Celiac disease risk in the USA: highprevalence of antiendomysium antibodies in healthy blood donors. ScandJ Gastroenterol 1998;33:494-8.19. Hill I, Fasano A, Schwartz R, Counts D, Glock M, Horvath K. Theprevalence of celiac disease in at-risk groups of children in the UnitedStates. J Pediatr 2000;136:86-90.20. Maki M, Holm K, Koskimies S, Hallstrom O, Visakorpi JK. Normalsmall bowel biopsy followed by coeliac disease. Arch Dis Child 1990;65:1137-41.21. Dieterich W, Ehnis T, Bauer M, et al. Identification of tissue trans-

glutaminase as the autoantigen of celiac disease. Nat Med 1997;3:797-801.22. Dieterich W, Laag E, Schopper H, et al. Autoantibodies to tissuetransglutaminase as predictors of celiac disease. Gastroenterology 1998;115:1317-21.23. Vitoria JC, Arrieta A, Arranz C, et al. Antibodies to gliadin, endomy-sium, and tissue transglutaminase for the diagnosis of celiac disease. J Pe-diatr Gastroenterol Nutr 1999;29:571-4.24. Yardley JH. Malabsorptive disorders. In: Ming S-C, Goldman H, eds.Pathology of the gastrointestinal tract. 2nd ed. Baltimore: Williams &

Wilkins, 1998:755-99.25. Leonard N, Feighery CF, Hourihane DO. Peptic duodenitis — doesit exist in the second part of the duodenum? J Clin Pathol 1997;50:54-8.26. Trier JS. Celiac sprue. N Engl J Med 1991;325:1709-19.27. Murray JA. The widening spectrum of celiac disease. Am J Clin Nutr1999;69:354-65.28. Logan RFA, Rifkind EA, Turner ID, Ferguson A. Mortality in celiacdisease. Gastroenterology 1989;97:265-71.

Copyright © 2001 Massachusetts Medical Society.

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DIARREA Y DESNUTRICION