CASE REPORT

Benign Small Bowel Thickening and Lymphadenopathy:A Manifestation of Celiac Disease

Jerry Martel Æ Daniel A. Sussman Æ Robert I. Goldberg ÆMichael Valantas Æ Jamie S. Barkin

Received: 14 April 2008 / Accepted: 25 June 2008 / Published online: 21 August 2008

� Springer Science+Business Media, LLC 2008

Introduction

Celiac disease (CD) is the most common familial gastroin-

testinal (GI) disorder with an overall prevalence of 1:250 [1].

Small bowel lymphoma with lymphadenopathy is a well-

documented complication of patients with CD [2]. It

accounts for one-half to two-thirds of malignancies com-

plicating CD [3, 4]. However, small bowel thickening with

lymphadenopathy does not always represent malignancy.

Several case reports suggest lymphadenopathy representing

benign disease in patients with CD, as there was subsequent

regression on a gluten-free diet in the majority of patients

[5–14]. We report three patients with small bowel thickening

with biopsy-proven CD and lymphadenopathy with sub-

sequent regression after appropriate treatment for CD.

Case Series

Patient 1 is a 40-year-old White woman referred with

episodes of abdominal pain. She described the pain as

intermittent, crampy, localized to the left lower quadrant of

the abdomen, and lasting 2–3 h. It did not improve with

passage of either gas or stool, nor was there any association

with food. She denied weight loss, change in appetite,

fever, chills, night sweats, or change in bowel habits. She

had been having one or two loose stools daily for her entire

life. A computed tomography (CT) scan performed of the

abdomen and pelvis showed mesenteric lymphadenopathy

with thickened small bowel and areas of intermittent

intussusception in the mid to distal jejunum which was

confirmed on small bowel series. Her physical examination

was unremarkable. Laboratory data was significant for

white blood cells (WBC) 6,200/ll, hemoglobin (Hgb)

13.3 g/dl, mean corpuscular volume (MCV) 89fl, total

protein 5.3 g/dl, and albumin 2.9 g/dl. She underwent an

exploratory laparoscopy for the abnormal CT findings with

biopsy of multiple mesenteric lymph nodes and resection

of a segment of jejunum. Pathology showed atypical small

bowel mucosa with villous blunting and lymphoplasma-

cytic infiltrate with reactive hyperplasia of the lymph

nodes. The pathology slides were reviewed by pathologists

at Johns Hopkins Reference Laboratories who confirmed

CD. Serologies drawn after the pathology results confirmed

CD with an IgA tissue transglutaminase (TTG) antibody

level of 25.4 AU (normal \7 AU) and qualitative IgA

antiendomysial antibodies (EMA) detected. Genetic studies

confirmed the presence of human leukocyte antigen (HLA)

DQ2 allele in the patient. Repeat CT scan at 2 months

showed complete regression of the lymphadenopathy after

the initiation of a gluten-free diet.

Patient 2 is a 76-year-old White man referred for eval-

uation of 40 pound weight loss over 4 months associated

with chronic diarrhea of 5 months’ duration. The patient

described the diarrhea as passage of multiple loose stools

daily with a nocturnal component and without any asso-

ciation to specific food or stress. He denied constipation,

J. Martel � D. A. Sussman � R. I. Goldberg � J. S. Barkin

University of Miami Miller School of Medicine, Miami,

FL, USA

J. Martel (&) � R. I. Goldberg � J. S. Barkin

Division of Gastroenterology, Mount Sinai Medical Center,

4300 Alton Road, Miami Beach, FL 33140, USA

e-mail: Jmartel3@med.miami.edu;

jerry.martel.md.mph@gmail.com

M. Valantas

Gastroenterology and Hepatology, Internal Medicine Associates,

LLC, Anchorage, AL, USA

123

Dig Dis Sci (2009) 54:902–905

DOI 10.1007/s10620-008-0426-4

abdominal pain, bloating, or distention. His physical

examination was unremarkable. Laboratory data was sig-

nificant for WBC 8,800/ll, Hgb 14.5 g/dl, MCV 100fl, and

alanine aminotransferase (ALT) 59 IU/l (normal 30–65 IU/

l), with the remainder of his laboratory data within normal

limits. Pathology from esophagogastroduodenoscopy

(EGD) revealed partial flattening of the villi with acute and

chronic inflammation. Colonoscopy was performed and

biopsies showed normal mucosa. Celiac antibodies were

positive for IgA antigliadin antibodies 6.2 U/ml (nor-

mal \5 U/ml) with genetic testing not performed due to

the presence of antibodies for CD. The patient was started

on a gluten-free diet for 2 months, but was nonadherent.

CT of the abdomen and pelvis at an outside institution

demonstrated mesenteric lymphadenopathy with focal

concentric thickening of the proximal small bowel loops.

Enteroscopy with biopsy revealed intestinal mucosa with

complete blunting of villi with increased intraepithelial

lymphocytes consistent with CD. Initiation of a strict glu-

ten-free diet provided mild improvement in symptoms and,

after a short course of glucocorticoid therapy, the patient’s

symptoms improved. Lymphoma was considered in the

differential diagnosis and whole body repeat CT scan at

3 months showed normal small bowel loops and

improvement in the lymphadenopathy (Fig. 1) and positron

emission tomography showed no significant uptake within

the lymph nodes.

Patient 3 is a 37-year-old White man with history of

testicular cancer in remission referred initially for evalua-

tion of rectal bleeding. The patient was diagnosed with an

anal fissure; however, upon further questioning, the patient

was found to have intermittent diarrhea for the last 2 years

with lymphadenopathy noted in prior CT scans. The patient

denied constipation, weight loss, abdominal pain, bloating,

or other complaints. Laboratory data was significant for

WBC 8,200/ll, Hgb 16.4 g/dl, MCV 91.9fl, ALT 35 IU/l

(normal 9–57 IU/l), glucose 131 mg/l, and CO2 22 mEq/l

(normal 23–35 mEq/l), with the remainder of his labora-

tory data within normal limits. CT of the abdomen and

pelvis 6 months prior demonstrated lymphadenopathy with

small bowel thickening with increase in the lymphade-

nopathy on CT repeated 3 months later. Celiac antibodies

were performed and found positive for IgA antiendomysial

antibodies with titer of 1:160 and IgA tissue transgluta-

minase of 79 (positive [8) with genetic testing not

performed due to the presence of antibodies for CD. Upper

GI endoscopy demonstrated patchy mild mucosal abnor-

mality with erythema in entire duodenum and pathology

demonstrating variable villous atrophy and increased

numbers of intraepithelial lymphocytes within surface

epithelium consistent with celiac sprue. After instituting a

gluten-free diet, repeat CT demonstrated reversion of the

small bowel thickening and decrease in the size of the

lymph nodes. The patient had a small bowel capsule ent-

eroscopy which demonstrated mucosal changes in the

distal jejunum and ileum.

Discussion

CD is a chronic inflammatory condition secondary to die-

tary exposure to gluten. This stimulation of the immune

Fig. 1 CT images of the

abdomen demonstrating LAD

(a) and SB thickening (b, c) and

3 months later demonstrating

resolving LAD and normal

caliber small bowel (d).

CT, computer tomography;

LAD, lymphadenopathy;

SB, small bowel

Dig Dis Sci (2009) 54:902–905 903

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system leads to reactive hyperplasia of lymphoid tissues

and atrophy of the bowel epithelium. Small bowel lym-

phoma is a well-known complication of CD. However,

increasing numbers of reports exist of benign lymphade-

nopathy as initial findings in undiagnosed CD [12]. The

increase in incidence may be related to the increased use of

radiologic modalities in the evaluation of abdominal

complaints. Our series shows that, in addition to lym-

phadenopathy, there can be thickening of the small bowel

and intussusception accompanied by lymphadenopathy

which simulate the findings of small bowel lymphoma

(Table 1). In addition, our reports corroborate the findings

of regression of lymph nodes with a gluten-free diet as a

result of removal of exposure of the inciting antigen [5–7].

It is important to determine radiologic characteristics of

lymphadenopathy to classify malignant versus benign dis-

ease in patients with CD including size, cavitation, and

location of lymph nodes. Reports of cavitation in lymph

node biopsies in patients with ulcerative enterocolitis

associated with CD [10] were benign in nature. Yousif and

others suggested that lymph nodes less than 1 cm and the

lack of systemic lymphadenopathy are indicators of benign

disease [7]. Harris reports the visualization of a clear

cleavage plane between the adenopathy and the great

vessels is preserved in benign disease [15]. However,

negative biopsies do not completely eliminate the possi-

bility of lymphoma as sampling error may be involved in

both the enteroscopic and the laparoscopic biopsies. One of

our patients underwent laparoscopy to evaluate for lym-

phoma of the small bowel as radiologic findings of

thickening with weight loss were highly worrisome and

suspicious for a malignant process. We recommend

patients continue with serial imaging to document regres-

sion of the lymphadenopathy on the gluten-free diet and

close follow-up for possible progression to lymphoma. Our

patients demonstrated regression on a gluten-free diet

whether or not laparoscopy was involved, but we agree

these patients need to be followed closely for the presence

or evolution of lymphoma.

In conclusion, benign lymphadenopathy and small bowel

thickening in CD likely will be discovered more frequently

as the use of imaging continues to grow and the quality

improves. We have presented the cases of three patients

with small bowel thickening and lymphadenopathy all

related to undiagnosed CD and its regression with a gluten-

free diet both with and without steroid therapy. The cases

presented suggest that lymphadenopathy associated with

thickened bowel can be observed and followed with a strict

gluten-free diet in patients with CD following initial biopsy.

The concern for an undiagnosed malignancy may cause

uneasiness in the clinician and patient, ultimately leading to

further evaluation with imaging and/or biopsy via EGD,

enteroscopy, double-balloon enteroscopy, or laparoscopy.

References

1. Not T, Horvath K, Hill ID, Partanen J, Hammed A, Magazzu G

et al (1998) Celiac disease risk in the USA: high prevalence of

antiendomysium antibodies in healthy blood donors. Scand J

Gastroenterol 33:494–498. doi:10.1080/00365529850172052

2. Freeman H, Lemoyne M, Pare P (2002) Coeliac disease. Best Pract

Res Clin Gastroenterol 16:37–49. doi:10.1053/bega.2002.0264

3. Corrao G, Corazza GR, Bagnardi V, Brusco G, Ciacci C, Cottone

M et al (2001) Mortality in patients with coeliac disease and their

Table 1 Patient demographics, findings, pathology results, and therapy

Patient

information

Patient A Patient B Patient C

Age, sex,

presentation

40-year-old woman with abdominal pain

and diarrhea

76-year-old man with weight loss and

diarrhea

37-year-old man with intermittent

diarrhea

CT scan

findings

Multiple prominent lymph nodes in left

abdominal mesentery; small bowel

thickening with partial transient

intussusception

Mild mesenteric lymphadenopathy and

thickening of a portion of the small

bowel

Nonspecific intra-abdominal

lymphadenopathy around the small

bowel which appears slightly

thickened

Diagnostic

modality

Diagnostic laparoscopy Enteroscopy and biopsy Enteroscopy and biopsy 9 2

Biopsy results Lymph node: reactive lymphoid

hyperplasia. Small bowel: small

intestinal mucosa with mild villous

blunting and striking intraepithelial

lymphocytosis

Small bowel: intestinal mucosa with

complete blunting of villi with

increased surface epithelial

lymphocytes consistent with sprue

Small bowel 1: benign small intestinal

mucosal tissue with preserved

villous architecture & prominent

lymphoid follicles

Small bowel 2: small bowel mucosa

with variable villous atrophy

consistent with CD

Positive

serologies

IgA tTG IgA EMA IgA EMA and IgA tTG

Management Gluten-free diet Gluten-free diet and prednisone Gluten-free diet

904 Dig Dis Sci (2009) 54:902–905

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relatives: a cohort study. Lancet 358:356–361. doi:10.1016/

S0140-6736(01)05554-4

4. Askling J, Linet M, Gridley G, Halstensen TS, Ekstrom K, Ekbom A

(2002) Cancer incidence in a population-based cohort of individuals

hospitalized with celiac disease or dermatitis herpetiformis. Gas-

troenterology 123(5):1428–1435. doi:10.1053/gast.2002.36585

5. de Boer WA, Maas M, Tytgat GN (1993) Disappearance of mes-

enteric lymphadenopathy with gluten-free diet in celiac sprue. J

Clin Gastroenterol 16(4):317–319. doi:10.1097/00004836-199306

000-00010

6. Al-Kawas FH, Murgo A, Foshag L, Shiels W (1988) Lymphad-

enopathy in celiac disease: not always a sign of lymphoma. Am J

Gastroenterol 83(3):301–303

7. Yousif E, Gupta R, Gelzayd E, Osher D, Maas L (1998) Lym-

phadenopathy in celiac sprue, not necessarily a malignant disease. J

Clin Gastroenterol 27(1):82–84. doi:10.1097/00004836-199807

000-00019

8. Jones PE, Gleeson MH (1973) Mucosal ulceration and mesenteric

lymphadenopathy in coeliac disease. BMJ 3(5873):212–213

9. Holmes GK (1986) Mesenteric lymph node cavitation in coeliac

disease. Gut 27(6):728–733. doi:10.1136/gut.27.6.728

10. Matuchansky C, Colin R, Hemet J, Touchard G, Babin P, Eugene

C et al (1984) Cavitation of mesenteric lymph nodes, splenic

atrophy, and a flat small intestinal mucosa: Report of six cases.

Gastroenterology 87(3):606–614

11. Howat AJ, McPhie JL, Smith DA, Aqel NM, Taylor AK, Cairns SA

et al (1995) Cavitation of mesenteric lymph nodes: a rare compli-

cation of coeliac disease, associated with a poor outcome.

Histopathology 27(4):349–354. doi:10.1111/j.1365-2559.1995.

tb01525.x

12. Jones B, Bayless TM, Fishman EK, Siegelman SS (1984) Lym-

phadenopathy in celiac disease: computed tomographic observations.

Am J Roentgenol 142(6):1127–1132

13. Simmonds JP, Rosenthal FD (1981) Lymphadenopathy in coeliac

disease. Gut 22(9):756–758. doi:10.1136/gut.22.9.756

14. Willingham FF, Opekun AR, Graham DY (2003) Endoscopic

demonstration of transient small bowel intussusception in a patient

with adult celiac disease. Gastrointest Endosc 57(4):626–627

15. Harris RD (1979) Computerized tomography of retroperitoneal

lymphadenopathy: benign or malignant. Comput Tomogr 3(2):73–

80. doi:10.1016/0363-8235(79)90001-2

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