Celiac disease or Sprue Celiac disease (CD) is a malabsorption syndrome characterized
by villous atrophy and crypt hyperplasia of the small intestinal mucosa. In
genetically susceptible individuals, there is a T-cell response to a new epitope
generated by the transglutaminase-mediated deamidization of dietary gliadin.
| DISEASE ASSOCIATIONS |
CHARACTERIZATION |
| DERMATITIS HERPETIFORMIS |
|
| GASTRIC HETEROTOPIA OF THE JEJUNUM |
|
| Severe Malabsorption due to Refractory Celiac Disease Complicated by Extensive Gastric Heterotopia of the Jejunum Tribl, Barbara MD*; Aschl, Gerhard MD†; Mitterbauer, Gerlinde MD‡; Novacek, Gottfried MD*; Vogelsang, Harald MD, PHD*; Chott, Andreas MD§
From the *Department of Internal Medicine IV, Division of Gastroenterology and Hepatology, the §Department of Pathology, the ‡Department of Laboratory Medicine, Vienna General Hospital, Vienna, and the †Krankenhaus der Barmherzigen Schwestern, Wels, Austria. |
The American Journal of Surgical Pathology : Volume 28(2) February 2004 pp 262-265 Abstract quote
Refractory celiac disease denotes that patients considered to have celiac disease fail to respond histologically to treatment with a gluten-free diet. Among several causes of nonresponsiveness, enteropathy-type T-cell lymphoma is most important because of its almost invariably rapid lethal outcome.
We present the case of a 44-year-old patient with refractory celiac disease complicated by unusually severe malabsorption. Repeated duodenal biopsies disclosed normal and slightly shortened villi, focal crypt hypertrophy, and a moderate increase of intraepithelial lymphocytes consistent with celiac disease, but unable to explain the severe malabsorption. To rule out cryptic lymphoma, push enteroscopy was done providing 21 biopsies taken along the entire jejunum. Surprisingly, about 70% of the biopsies were composed of gastric glands covered by nonabsorptive-type, strongly periodic acid-Schiff-positive surface epithelium and showed a villous architecture. Alternating with the gastric mucosa, there were areas of flat mucosa with elongated crypts and occasional erosions. Irrespective of the type of surface epithelium, intraepithelial lymphocytes were increased with counts up to 80/100 epithelial cells.
Despite harboring an aberrant immunophenotype, overt T-cell lymphoma was ruled out histologically and by lack of monoclonality, as tested by polymerase chain reaction. To the best of our knowledge, this is the first case of refractory celiac disease complicated by extensive jejunal gastric heterotopia, which might have contributed to the severe malabsorption. |
| IRON DEFICIENCY ANEMIA |
|
| LYMPHOCYTIC COLITIS |
|
| LYMPHOCYTIC GASTRITIS |
|
| MYOCARDITIS |
|
|
Celiac disease associated with autoimmune myocarditis.
Frustaci A, Cuoco L, Chimenti C, Pieroni M, Fioravanti G, Gentiloni
N, Maseri A, Gasbarrini G.
Department of Cardiology, Catholic University, Rome, Italy.
|
Circulation 2002 Jun 4;105(22):2611-8 Abstract quote
BACKGROUND: Both celiac disease (CD) and myocarditis can be associated
with systemic autoimmune disorders; however, the coexistence of the
2 entities has never been investigated, although its identification
may have a clinical impact.
METHODS AND RESULTS: We screened the serum of 187 consecutive patients
with myocarditis (118 males and 69 females, mean age 41.7+/-14.3 years)
for the presence of cardiac autoantibodies, anti-tissue transglutaminase
(IgA-tTG), and anti-endomysial antibodies (AEAs). IgA-tTG-positive and
AEA-positive patients underwent duodenal endoscopy and biopsy and HLA
analysis. Thirteen of the 187 patients were positive for IgA-tTG, and
9 (4.4%) of them were positive for AEA. These 9 patients had iron-deficient
anemia and exhibited duodenal endoscopic and histological evidence of
CD. CD was observed in 1 (0.3%) of 306 normal controls (P<0.003).
In CD patients, myocarditis was associated with heart failure in 5 patients
and with ventricular arrhythmias (Lown class III-IVa) in 4 patients.
From histological examination, a lymphocytic infiltrate was determined
to be present in 8 patients, and giant cell myocarditis was found in
1 patient; circulating cardiac autoantibodies were positive and myocardial
viral genomes were negative in all patients. HLA of the patients with
CD and myocarditis was DQ2-DR3 in 8 patients and DQ2-DR5(11)/DR7 in
1 patient. The 5 patients with myocarditis and heart failure received
immunosuppression and a gluten-free diet, which elicited recovery of
cardiac volumes and function. The 4 patients with arrhythmia, after
being put on a gluten-free diet alone, showed improvement in the arrhythmia
(Lown class I).
CONCLUSIONS: A common autoimmune process toward antigenic components
of the myocardium and small bowel can be found in >4% of the patients
with myocarditis. In these patients, immunosuppression and a gluten-free
diet can be effective therapeutic options. |
| OSTEOPOROSIS |
|
| Prevalence of undiagnosed coeliac syndrome
in osteoporotic women.
Nuti R, Martini G, Valenti R, Giovani S, Salvadori
S, Avanzati A.
Institute of Internal Medicine, Metabolic Disease
Unit, University of Siena, Siena, Italy. |
J Intern Med 2001 Oct;250(4):361-6 Abstract quote
OBJECTIVES: The aims of the study were to quantify the prevalence of
asymptomatic coeliac disease (CD) in a cohort of osteoporotic females,
and to investigate the features of bone loss. Design and subjects. We
studied 255 women (mean age 66.6 +/- 8.5 SD) with primary osteoporosis
(WHO diagnostic criteria). After the first CD screening with the measure
of serum IgG antigliadin antibodies (IgG-AGA), 53 women showed a positive
test: antibodies to tissue transglutaminase (TG-ab) were subsequently
determined to confirm the diagnosis of CD. Bone metabolism was evaluated
by: serum and urinary calcium, serum and urinary phosphate, serum alkaline
phosphatase, urinary crosslaps, serum 25(OH)D and serum parathyroid
hormone.
RESULTS: High levels of IgG-AGA and TG-ab were observed in 24 patients
with a prevalence of serological disease of 9.4%. These women were characterized,
in comparison with the other patients, by a statistically significant
reduction in serum 25(OH)D (17.8 +/- 7.2 vs. 55.1 +/- 20.3 nmol L-1,
P < 0.01) together with a significant increase of iPTH (65.1 +/- 29.7
vs. 35.1 +/- 20.0 pg mL-1; P < 0.01). Patients with high TG-ab levels
showed also slightly raised values of urinary crosslaps (288 +/- 88
vs. 270 +/- 90 &mgr;m mol-1 Cr). In IgG-AG positive patients a statistically
significant inverse correlation was found between 25(OH)D serum levels
and log-transformed TG-ab values (r: -0.95, P < 0.001). Intestinal biopsies
were obtained in 10 TG-ab positive women and verified CD in six patients.
CONCLUSIONS: These data support the hypothesis that patients with undiagnosed
celiac disease develop high remodelling processes related to calcium
malabsorption, secondary hyperparathyroidism and unavailability of vitamin
D with a consequent more marked bone loss. |
| Selective IgA deficiency |
|
| Insulin dependent diabetes mellitus |
|
| Sjogren's syndrome |
|
| Autoimmune thyroiditis |
|
| PATHOGENESIS |
CHARACTERIZATION |
| HLA |
Predominance of HLA DQ2 and/or DQ8 |
|
Genomewide Linkage Analysis of Celiac Disease in Finnish
Families.
Liu J, Juo SH, Holopainen P, Terwilliger J, Tong X,
Grunn A, Brito M, Green P, Mustalahti K, Maki M, Gilliam TC, Partanen
J.
Columbia Genome Center, Columbia University, New York,
New York, USA |
Am J Hum Genet 2001 Nov 19;70(1) Abstract quote
Celiac disease (CD), or gluten-sensitive enteropathy, is a common multifactorial
disorder resulting from intolerance to cereal prolamins. The only established
genetic susceptibility factor is HLA-DQ, which appears to explain only
part of the overall genetic risk.
We performed a genomewide scan of CD in 60 Finnish families. In addition
to strong evidence for linkage to the HLA region at 6p21.3 (Zmax>5),
suggestive evidence for linkage was found for six other chromosomal
regions-1p36, 4p15, 5q31, 7q21, 9p21-23, and 16q12. We further analyzed
the three most convincing regions-4p15, 5q31, and 7q21-by evaluation
of dense marker arrays across each region and by analysis of an additional
38 families. Although multipoint analysis with dense markers provided
supportive evidence (multipoint LOD scores 3.25 at 4p15, 1.49 at 5q31,
and 1.04 at 7q21) for the initial findings, the additional 38 families
did not strengthen evidence for linkage. The role that HLA-DQ plays
was studied in more detail by analysis of DQB1 alleles in all 98 families.
All but one patient carried one or two HLA-DQ risk alleles, and 65%
of HLA-DQ2 carriers were affected.
Our study indicates that the HLA region harbors a predominant CD-susceptibility
locus in these Finnish families. |
|
Tissue trans-glutaminase selectively modifies gliadin peptides that
are recognized by gut-derived T cells in celiac disease.
Molberg Ø, Mcadam SN, Korner R, et al. |
Nat Med. 1998;4:713-717. |
|
Increased Enterocyte Apoptosis and Fas-Fas Ligand System in Celiac
Disease
Rachele Ciccocioppo, etal. |
Am J Clin Pathol 2001;115:494-503 Abstract quote
Our aim was to evaluate whether increased enterocyte apoptosis was
responsible for mucosal flattening in celiac disease (CD), and, since
the mechanisms responsible for tissue injury in this condition are unknown,
we studied the possibility that the Fas-Fas ligand (FasL) system may
be involved.
Endoscopic duodenal biopsy specimens from 12 patients with untreated
and 12 with treated CD and 12 control subjects were evaluated for enterocyte
apoptosis by the terminal deoxynucleotidyl transferase–mediated digoxigenin-deoxyuridine
triphosphate nick-end labeling assay and for Fas and FasL expression
by immunohistochemistry. A coculture of isolated enterocytes (targets)
and purified lamina propria mononuclear cells (LPMCs) (effectors) was
performed in the absence or presence of an antagonistic ZB4 anti-Fas
antibody.
We found a significant correlation between the degree of villous atrophy,
morphometrically evaluated, and the level of enterocyte apoptosis, suggesting
that mucosal flattening is a consequence of exaggerated epithelial cell
death. Most celiac enterocytes express Fas, and LPMCs express FasL.
The abolishment of enterocyte apoptosis observed in the presence of
ZB4 antibody suggests that enterocytes are potential targets of lymphocyte
infiltrate.
These results directly demonstrate that FasL-mediated apoptosis is
a major mechanism responsible for enterocyte death in CD. |
|
Frequency of clonal intraepithelial T lymphocyte proliferations
in enteropathy-type intestinal T cell lymphoma, coeliac disease, and
refractory sprue.
Daum S, Weiss D, Hummel M, Ullrich R, Heise W, Stein H, Riecken
EO, Foss HD.
Medical Clinic I, Gastroenterology and Infectious Diseases, Universitatsklinikum
Benjamin Franklin, Free University of Berlin, Hindenburgdamm 30, 12200
Berlin, Germany. |
Gut 2001 Dec;49(6):804-12 Abstract quote
BACKGROUND: Clonal T cell receptor (TCR) gene rearrangements and loss
of T cell antigens such as CD8 and TCR-beta in intraepithelial lymphocytes
(IELs) may indicate the development of an enteropathy-type intestinal
T cell lymphoma (EITCL) in patients with refractory sprue.
AIMS: To define the diagnostic value of these markers in duodenal biopsies
from patients with villous atrophy as a result of various underlying
disorders. PATIENTS AND
METHODS: Duodenal biopsies from eight patients with coeliac disease
and five patients with villous atrophy caused by defined disorders were
compared with three patients with refractory sprue evolving into overt
EITCL, two patients with ulcerative jejunitis, and with eight patients
with overt EITCL, for expression of CD3, CD4, CD8, and TCR-beta in IELs
using immunohistochemistry and for clonal TCR-gamma gene rearrangements
using polymerase chain reaction. In addition, biopsies from six consecutive
patients with refractory sprue of uncertain cause were examined.
RESULTS: Clonal TCR-gamma gene rearrangements were found in all resected
tumours of patients with EITCL, in 3/8 duodenal biopsies of patients
with EITCL, in 2/2 patients with ulcerative jejunitis, in 2/3 patients
with refractory sprue evolving into overt EITCL, and in 1/6 patients
with refractory sprue. No rearrangements were found in biopsies from
patients with refractory sprue caused by defined disorders or those
with coeliac disease. Clonality in duodenal biopsies was associated
with an abnormal phenotype of IELs in all cases and in all but one case
in patients with evidence of underlying coeliac disease. Specificity
for detection of an EITCL using immunohistology was 77% for CD8 and
for TCR-beta staining, and 100% for detection of a clonal TCR-gamma
gene rearrangement. Sensitivity was 62% for staining with CD8 and clonality
investigation, while sensitivity reached 100% for TCR-beta staining
in all investigated patients with EITCL.
CONCLUSIONS: Clonal proliferations of phenotypically abnormal IELs
in refractory sprue represent an early manifestation of EITCL, for which
the term "sprue-like intestinal T cell lymphoma" is proposed. This constellation
is also found in duodenal biopsies from patients with an overt EITCL
and is not related to other sprue syndromes, resulting in a high specificity
for detection of an EITCL or refractory sprue evolving into EITCL. Overt
EITCL may develop directly from coeliac disease without a precursor
lesion (refractory sprue with clonal IELs) being demonstrable in duodenal
biopsies or via a "sprue-like intestinal T cell lymphoma". This latter
entity is a complication of coeliac disease. |
| EPITHELIAL JUNCTIONAL PROTEINS-ABNORMALITIES |
|
Altered Expression, Localization, and Phosphorylation of Epithelial Junctional Proteins in Celiac Disease
Rachele Ciccocioppo, MD, etal.. |
Am J Clin Pathol 2006;125:502-511
Abstract quote
We aimed to study the expression and localization of the molecular components of enterocyte junctions in celiac disease together with the level of tyrosine phosphorylation, a phenomenon known to affect their cellular distribution and function, and to explore the influence of proinflammatory cytokines.
Duodenal biopsy specimens from patients with celiac disease and control subjects were used for immunoprecipitation, immunoblotting, and immunolocalization by using antioccludin, anti–zonula occludens (ZO)-1, anti– E-cadherin, anti–b-catenin, and antiphosphotyrosine antibodies. The same procedures were carried out on filter-grown Caco-2 cells incubated in the absence or presence of interferon g and tumor necrosis factor a. In active celiac disease, the absence of a phosphorylated ZO-1 and the extensive phosphorylation of b-catenin might be responsible for the absence of membranous localization of occludin and E-cadherin, respectively.
The in vitro system showed an influence of the cytokines on the assembly of these complexes that proved the opposite to celiac samples as far as tight junctions were concerned because the presence of a phosphorylated ZO-1 enables occludin to localize in the membrane.
|
LABORATORY/
RADIOLOGIC/
OTHER TESTS |
CHARACTERIZATION |
| GENERAL |
|
|
Antibodies against human tissue transglutaminase and endomysium in diagnosing
and monitoring coeliac disease.
Burgin-Wolff A, Dahlbom I, Hadziselimovic F, Petersson CJ.
Institute for Coeliac Disease, Liestal, Switzerland. a.buergin- |
Scand J Gastroenterol. 2002 Jun;37(6):685-91 Abstract quote BACKGROUND:
Coeliac disease (CD) patients often present a variety of uncharacteristic
symptoms and therefore sensitive and specific screening tests are needed
as an aid in making an accurate diagnosis. A recently developed ELISA,
using human recombinant tissue transglutaminase (tTG) as antigen, was
evaluated for its significance in the diagnosis of CD. The patient's
compliance to a gluten-free diet and the serological reaction during
gluten challenge were also monitored. The results were compared with
IgA-endomysium antibody (EMA) results.
METHODS: Sera previously collected from 365 patients (0.4-76 years)
with jejunal biopsy on a gluten-containing diet and from 41 patients
on a gluten-free diet or challenge were tested for IgA anti-human tTG
antibodies (IgA tTG ab) with Celikey (Pharmacia Diagnostics). The study
population comprised 208 CD patients and 157 controls. The diagnostic
performance and cut-off for the assay were estimated with ROC analysis.
EMA was analysed by indirect immunofluorescence microscopy on cryostat
sections of monkey oesophagus.
RESULTS: 200/208 patients with CD had positive IgA tTG ab (median >100
U/ml), while only 1/157 of the control patients were positive (median
1.67 U/ml). The area under the ROC curve was 98.3% and the sensitivity
and specificity of the test were 96% and 99% for the study population.
Only 4/365 patients (1%) presented discordant IgA tTG ab and EMA results,
2 of them had only IgA tTG ab and 2 only EMA. The IgA tTG ab levels
and the EMA titres were closely correlated to the duration of gluten-free
diet and gluten challenge, respectively.
CONCLUSION: IgA tTG ab can be used as an accurate observer-independent
alternative to EMA in diagnosing or monitoring CD. |
Comparative evaluation of serologic tests for celiac disease: a European
initiative toward standardization.
Stern M; Working Group on Serologic Screening for Celiac Disease.
University Children's Hospital, Tubingen, Germany |
J Pediatr Gastroenterol Nutr 2000 Nov;31(5):513-9 Abstract quote
BACKGROUND: Serologic methods have been used widely to test for celiac
disease and have gained importance in diagnostic definition and in new
epidemiologic findings. However, there is no standardization, and there
are no reference protocols and materials.
METHODS: The European working group on Serological Screening for Celiac
Disease has defined robust noncommercial test protocols for immunoglobulin
(Ig)G and IgA gliadin antibodies and for IgA autoantibodies against
endomysium and tissue transglutaminase. Standard curves were linear
in the decisive range, and intra-assay variation coefficients were less
than 5% to 10%. Calibration was performed with a group reference serum.
Joint cutoff limits were used. Seven laboratories took part in the final
collaborative study on 252 randomized sera classified by histology (103
pediatric and adult patients with active celiac disease, 89 disease
control subjects, and 60 blood donors).
RESULTS: IgA autoantibodies against endomysium and tissue transglutaminase
rendered superior sensitivity (90% and 93%, respectively) and specificity
(99% and 95%, respectively) over IgA and IgG gliadin antibodies. Tissue
transglutaminase antibody testing showed superior receiver operating
characteristic performance compared with gliadin antibodies. The K values
for interlaboratory reproducibility showed superiority for IgA endomysium
(0.93) in comparison with tissue transglutaminase antibodies (0.83)
and gliadin antibodies (0.82 for IgG, 0.62 for IgA).
CONCLUSIONS: Basic criteria of standardization and quality assessment
must be fulfilled by any given test protocol proposed for serologic
investigation of celiac disease. The working group has produced robust
test protocols and reference materials available for standardization
to further improve reliability of serologic testing for celiac disease. |
Comparison of IgA endomysium antibody and IgA tissue transglutaminase
antibody in celiac disease.
Gillett HR, Freeman HJ.
Department of Medicine, University of British Columbia, Vancouver.
|
Can J Gastroenterol. 2000 Sep;14(8):668-71 Abstract quote The antigen
for immunoglobulin (Ig) A endomysium antibody (EmA), a sensitive and
specific serological marker for celiac disease, has recently been described
as tissue transglutaminase (tTG).
The aim of this study was to compare the assays used to measure IgA
EmA and IgA tTG antibody in patients with celiac disease and disease
control subjects. Sera from 21 patients with untreated celiac disease,
48 patients with treated celiac disease and 128 disease control subjects
were tested both for IgA EmA with the use of indirect immunofluorescence
against human umbilical cord and for IgA tTG antibody with the use of
ELISA.
Titres of IgA tTG antibody were significantly higher in both the untreated
and treated celiac groups than in the disease control group. Titres
in the treated group were, however, significantly lower than in the
untreated group. A reference range was calculated to include 99.8% of
the disease control group in whom small bowel biopsy showed no evidence
of celiac disease. One patient from the disease control group with raised
IgA tTG antibody titres and positive IgA EmA was found to have celiac
disease on small bowel biopsy.
The sensitivity, specificity, and positive and negative predictive values
of the IgA EmA assay were all 100%. The sensitivity of the IgA tTG antibody
assay was 95%, specificity 100%, positive predictive value 100% and
negative predictive value 97.7%. An ELISA used to measure IgA tTG antibody
is an excellent tool to screen for celiac disease and may prove useful
for monitoring response to treatment. |
| SERUM ANTIENDOYSIUM TITERS |
J Pediatr Gastroenterol Nutr 1998;27:191-195
More specific than antigliadin titers
However, may not be optimally sensitive in patients with architecturally
normal villi since it is present only with villus injury or flat mucosa |
| Antiendomysial antibody test reliability in children with frequent
diarrhea and malnutrition: is it celiac disease?
Gandolfi L, Catassi C, Garcia S, Modelli IC, Campos Jr D, Pratesi
R.
Departments of Pediatrics, University of Brasilia School of Medicine,
Brasilia, Brazil, and Department of Pediatrics, University of Ancona,
Italy. |
J Pediatr Gastroenterol Nutr 2001 Oct;33(4):483-7 Abstract quote
BACKGROUND: The aim of this study was to evaluate the specificity of
the immunoglobulin A (IgA) antiendomysial antibody test in the diagnosis
of celiac disease in a group of malnourished children with acute diarrhea,
chronic diarrhea, or parasitosis, because the reliability of this test
has been questioned when applied to this specific group of patients.
METHODS: Serum IgA level, IgA antiendomysial antibody (EMA) test,
and stool examination were performed in 315 children, ranging in age
6 months to 13 years (range, 41 +/- 2.9 months), affected by malnutrition,
isolated or in association with diarrhea or parasitosis. Independent
of results, 33 children with a strong suspicion of celiac disease, also
underwent IgA antitransglutaminase antibody test and jejunal biopsy.
RESULTS: The EMA test was negative in 313 children, including the 43
with parasitosis, being positive in two patients in whom biopsy disclosed
typical celiac mucosal abnormalities (1:157). The 31 children with negative
EMA test who underwent biopsy also showed negative antitransglutaminase
antibody results. Their biopsies disclosed normal mucosa in 1 patient,
variable degree of jejunal atrophy (grade 1 and 2) in 27 patients, and
grade 3 abnormalities in 3 patients. One of these three children, showing
severe jejunal atrophy, died. The diagnosis of celiac disease was apparently
not confirmed by a protracted gluten challenge in the other two children.
CONCLUSIONS: The specificity of the EMA test seems to be high also
in children with chronic malnutrition and diarrhea. However, the possibility
of false-negative tests among immunologically compromised children cannot
be excluded. In doubtful cases, the gluten challenge is required in
malnourished children with clinical picture, biopsy finding, and evolution
suggestive of celiac disease. |
| TISSUE TRANSGLUTAMINASE AUTOANTIBODY |
|
The role of antitissue transglutaminase assay for the diagnosis and monitoring
of coeliac disease: a French-Italian multicentre study. Tonutti
E, Visentini D, Bizzaro N, Caradonna M, Cerni L, Villalta D, Tozzoli
R; French-Italian Laboratory Study Group on Coeliac Disease.
Istituto di Chimica Clinica, Azienda Ospedaliera S. Maria della
Misericordia, 33100 Udine, Italy.
|
J Clin Pathol. 2003 May;56(5):389-93 Abstract quote AIMS: Tissue
transglutaminase (tTG) was recently identified as the major autoantigen
in coeliac disease. The aim of this multicentre study was to evaluate
the impact of a new immunoenzymatic assay for the detection of IgA anti-tGT
antibodies.
METHODS: Seventy four Italian and French clinical laboratories participated
in this study; anti-tTG IgA with an enzyme linked immunosorbent assay
(ELISA) method using guinea pig liver extract as the coating antigen,
anti-endomysium IgA autoantibodies (EMA), and total serum IgA were determined
in 7948 patients, 1162 of whom had coeliac disease (737 untreated cases
and 425 on a gluten free diet). A proportion of the sera were then sent
to a reference laboratory for anti-tTG retesting with an ELISA method
using recombinant human tTG antigen.
RESULTS: Seven thousand four hundred and fifty eight (93.8%) sera were
EMA/antiguinea pig tTG concordant (positive or negative); 490 (6.2%)
were non-concordant. The sensitivity of EMA and antiguinea pig tTG in
the 737 untreated patients with coeliac disease was 92.1% and 94.8%,
respectively, and the specificity was 99.8% and 99.2%, respectively.
Retesting of the discordant sera showed that of the 162 sera classified
as EMA negative/antiguinea pig tTG positive, only 49 were positive for
human recombinant anti-tTG, and that 39 of these were also EMA positive.
Furthermore, of the 36 sera classified as EMA positive/antiguinea pig
tTG negative, only two were confirmed as EMA positive.
CONCLUSIONS: The antiguinea pig tTG assay is more sensitive but less
specific than EMA, whereas the antihuman recombinant tTG assay is far
more specific and just as sensitive as antiguinea pig tTG. Testing for
EMA presents considerable interpretative problems and is difficult to
standardise.
|
Antibodies to human recombinant tissue transglutaminase may detect coeliac
disease patients undiagnosed by endomysial antibodies.
Tesei N, Sugai E, Vazquez H, Smecuol E, Niveloni S, Mazure
R, Moreno ML, Gomez JC, Maurino E, Bai JC.
'Dr Carlos Bonorino Udaondo' Gastroenterology Hospital, Del
Salvador University, Buenos Aires, Argentina; USNMA, San Martin Hospital,
La Plata, Argentina.
|
Aliment Pharmacol Ther. 2003 Jun 1;17(11):1415-23 Abstract quote BACKGROUND:
The screening and diagnosis of coeliac disease have been simplified
by the advent of new serological tools. AIM: To assess the clinical
utility of a newly developed kit for antibodies to human recombinant
tissue transglutaminase (hu-anti-tTG) in a large population of patients
undergoing intestinal biopsy for suspected intestinal disorders.
METHODS: We evaluated 426 serum samples from consecutive adult patients
(250 from untreated coeliac disease patients and 176 from individuals
in whom a diagnosis of coeliac disease had been excluded), obtained
at the time of intestinal biopsy. Samples were tested for immunoglobulin
A (IgA) hu-anti-tTG by enzyme-linked immunoabsorbent assay, IgA endomysial
antibodies (EmA) by indirect immunofluorescence and IgA and IgG antigliadin
antibodies by enzyme-linked immunoabsorbent assay. A sub-group of samples
was also assessed for a guinea-pig-based anti-tissue transglutaminase.
RESULTS: According to the cut-off for hu-anti-tTG, the sensitivity,
specificity and positive and negative predictive values were 91%, 96%,
97% and 87%, respectively. Simultaneous determination of EmA showed
values of 86%, 100%, 100% and 83% for the same parameters. Although
19 coeliac disease patients (7.6%) were negative for EmA and hu-anti-tTG,
both tests rendered superior statistical values to antigliadin antibody
tests. At diagnosis, IgA deficiency was detected in 11 patients, but
both assays were able to detect samples with mild to moderate deficiency.
The comparison of hu-anti-tTG with EmA showed excellent concordance
between the tests (kappa statistic, 0.85). Discordance was observed
in 20 samples from coeliac disease patients (8%) and in nine samples
from controls (5%). Fifteen samples had an EmA-negative but hu-anti-tTG-positive
serology, and five showed the converse pattern. Comparison of human
recombinant and guinea-pig tests showed concordant results in 96% of
cases.
CONCLUSIONS: The quantitative determination of hu-anti-tTG type IgA
using a commercial enzyme-linked immunoabsorbent assay kit was highly
sensitive and specific for the detection of coeliac disease. Our results
in a large population of patients with a clinical condition suggestive
of the disorder demonstrated that the test can be used to detect a substantial
number of patients otherwise unrecognized by IgA EmA.
|
| Tissue transglutaminase autoantibody enzyme-linked
immunosorbent assay in detecting celiac disease.
Sulkanen S, Halttunen T, Laurila K, Kolho KL, Korponay-Szabo IR,
Sarnesto A, Savilahti E, Collin P, Maki M.
Institute of Medical Technology, University of Tampere, Tampere,
Finland. |
Gastroenterology 1998 Dec;115(6):1322-8 Abstract quote
AIMS: Tissue transglutaminase has been reported to be the target for
endomysial antibodies in celiac disease. We sought to establish whether
immunoglobulin (Ig) A class tissue transglutaminase autoantibodies can
be considered specific for celiac disease.
METHODS: Serum samples from 136 patients with untreated celiac disease
(diagnosed according to the criteria of the European Society for Pediatric
Gastroenterology, Hepatology and Nutrition) and 207 disease controls
were studied. Enzyme-linked immunosorbent assay (ELISA) and Western
blots were performed using calcium-treated and untreated tissue transglutaminase
as antigen. Reticulin, endomysial, and mouse monoclonal tissue transglutaminase
antibodies were studied by an indirect immunofluorescence method and
gliadin antibodies with ELISA.
RESULTS: The calcium-activated tissue transglutaminase autoantibody
ELISA was highly sensitive (129 of 136) and specific (194 of 207) in
detecting celiac disease. The new autoantibody ELISA test correlated
well with the endomysial antibody test. Tissue transglutaminase autoantibody
ELISA showed a clearly better predictive potential than the IgA class
gliadin antibody ELISA. Immunoblots and ELISA blocking studies showed
that calcium is needed for the specific antigen-antibody reaction to
occur. Double immunofluorescence staining in human umbilical cord with
sera from patients with celiac disease and with monoclonal tissue transglutaminase
antibodies showed complete overlap.
CONCLUSIONS: Calcium-activated tissue transglutaminase autoantibody
ELISA is highly accurate in detecting untreated celiac disease. Tissue
transglutaminase seems to be the target self-antigen for endomysial
antibodies. |
| HISTOLOGICAL TYPES |
CHARACTERIZATION |
| General |
|
| Morphologic Features Suggestive of Gluten Sensitivity
in Architecturally Normal Duodenal Biopsy Specimens
Neal S. Goldstein, MD, and Jeanette Underhill, MD |
Am J Clin Pathol 2001;116:63-71 Abstract quote
We studied small bowel biopsy specimens with architecturally normal
villi from 78 adult patients with potential gluten sensitivity (GS)
and correlated them with outcome to characterize morphologic features
that would allow a pathologist to suggest GS.
No patient had a previous GS diagnosis. Twelve study patients had GS.
The mean number of intraepithelial lymphocytes (IELs) per 20 enterocytes
from the tips of 5 random villi was significantly greater in GS than
non-GS biopsy samples, but the groups overlapped significantly, making
the number diagnostically useful only when markedly increased. Crypt
mitoses counts had similar relationships. Twelve patients had an even
distribution of IELs along villus sides and over tips (3/66 [5%] non-GS
patients, 9/12 [75%] GS patients). Non-GS patients had a decrescendo
pattern of IELs along the sides of villi. Architecturally normal small
bowel biopsy specimens with an appreciable, continuous, even distribution
of IELs along the sides and tips of villi and a mean of 12 or more IELs
in the tips of several villi are suggestive of GS. Pathologists should
be watchful for these morphologic features in small bowel biopsy specimens
to suggest GS. |
| VARIANTS |
|
| The Histologic Spectrum and Clinical Outcome of Refractory
and Unclassified Sprue Marie E. Robert, M.D.; Marvin E. Ament,
M.D.; Wilfred M. Weinstein, M.D.
Department of Pathology (M.E.R), Yale University School of Medicine,
New Haven, Connecticut, U.S.A.; Departments of Pediatrics (M.E.A.) and
Medicine (W.M.W.), University of California, Los Angeles, Center for
Health Sciences, Los Angeles, California, U.S.A. |
Am J Surg Pathol 2000;24:676-687 Abstract quote
The vast majority of patients with celiac disease respond to a gluten-free
diet; yet, a small number of refractory patients do not respond and
have persistent malabsorption and residual mucosal abnormalities of
the small intestine. The histologic features of refractory/unclassified
sprue have been published as case reports, often without long-term follow
up, and no clear histologic picture has emerged.
We present the results of a long-term study of the clinical and histologic
features of 10 patients with refractory/unclassified sprue.
The histologic features of small bowel biopsies in this group of patients
were compared with those of 10 patients with responsive celiac disease
and with 10 patients without malabsorption who had normal duodenal biopsies.
Five of the 10 refractory patients ultimately developed collagenous
sprue as a distinct histologic marker of refractory disease. Additional
distinctive findings found in small bowel biopsies in the refractory
group were subcryptal chronic inflammation (10 of 10) and marked mucosal
thinning in three patients. Other nonspecific findings included acute
inflammation and gastric metaplasia. One patient with collagenous sprue
developed a B-cell lymphoma of the ileum, and in general collagenous
sprue was associated with a poor prognosis. Two of five patients died
whereas two others require total parenteral nutrition for survival.
Pathologists evaluating small bowel biopsies in the setting of malabsorption
should be aware of the subtle histologic changes described here that
may portend a refractory course. |
| TREATMENT-POST |
|
|
Histologic follow-up of people with celiac disease on a gluten-free
diet: slow and incomplete recovery.
Wahab PJ, Meijer JW, Mulder CJ.
Department of Gastroenterology and Hepatology, Rijnstate Hospital
Arnhem, The Netherlands. |
Am J Clin Pathol 2002 Sep;118(3):459-63 Abstract quote
To assess histologic recovery in response to gluten withdrawal in celiac
disease, 158 patients seen in our hospital during a 15-year period underwent
follow-up small intestine biopsies (SIBs) within 2 years after starting
a gluten-free diet; further SIBs were done if villous atrophy was present.
A modified Marsh classification was used (IIIA, partial villous atrophy;
IIIB, subtotal villous atrophy; IIIC, total villous atrophy). Of patients
with Marsh IIIA, IIIB, or IIIC lesions, histologic remission was seen
in 65.0% within 2 years, 85.3% within 5 years, and 89.9% in long-term
follow-up. Eleven patients (7.0%) with persisting (partial) villous
atrophy had symptoms and signs of malabsorption and were considered
to have refractory celiac disease; 5 of them developed an enteropathy-associated
T-cell lymphoma. Children recovered up to 95% within 2 years and 100%
in the long-term.
Histologic recovery in celiac disease after starting a gluten-free
diet takes time and is incomplete or absent in a substantial subgroup
of patients (10.1% villous atrophy after 5 years). Systematic follow-up
of patients with celiac disease and the malabsorption syndrome and secondary
complications is needed. |
| STOMACH |
|
Characterization of gastric mucosal lesions in patients with celiac
disease: a prospective controlled study.
Diamanti A, Maino C, Niveloni S, Pedreira S, Vazquez H, Smecuol
E, Fiorini A, Cabanne A, Bartellini MA, Kogan Z, Valero J, Maurino E,
Bai JC.
Small Bowel Section, Clinical Service, Hospital de Gastroenterologia,
Dr. Carlos Bonorino Udaondo, Universidad del Salvador, Buenos Aires,
Argentina.
|
Am J Gastroenterol 1999 May;94(5):1313-9 Abstract quote
OBJECTIVE: Several studies have demonstrated that chronic exposure
to gluten may damage the structure and function of the gastric mucosa
in gluten-sensitive patients. However, until now, these abnormalities
have been incompletely studied. Our purpose in the present study was
to characterize, in a prospective controlled study, the endoscopic and
histological appearance of the gastric mucosa in a large cohort of patients
with celiac disease with and without Helicobacter pylori (H. pylori)
infection.
METHODS: We evaluated biopsy specimens taken from the gastric body
and antrum of 218 individuals who underwent upper endoscopy for small
bowel biopsy. One hundred-four patients had celiac disease (80 of them
at the time of diagnosis-untreated). In 114 subjects celiac disease
was excluded.
RESULTS: Endoscopic findings did not show a difference between the
groups. The prevalence of cases with normal gastric mucosa, chronic
superficial gastritis, and atrophic gastritis was similar in patients
and controls. Similarly, presence of metaplasia, inflammatory activity,
and lymphoid follicles and aggregates did not show differences between
the groups. Histological or serological evidence of H. pylori infection
was detected in 86% of patients (82% of untreated celiacs and 95% of
those on those taking treatment). The infection was highly prevalent
in patients (89%) and controls (97%) diagnosed with chronic gastritis.
Untreated patients had a significant greater IEL count in the antrum
and corpus than controls (p < 0.0001 and p < 0.001, respectively).
A global analysis of the data on intraepithelial lymphocyte (IEL) counts
in the different populations suggest that the inflammatory state may
represent the cumulative effect of H. pylori infection and gluten sensitivity.
Only three patients had IEL infiltration compatible with diagnosis of
lymphocytic gastritis (count >25%) and three other patients had borderline
counts.
CONCLUSIONS: According to our results, celiac disease patients presented
a similar prevalence of gastric mucosal abnormalities compared with
the control population. Evidence of H. pylori infection was very high
compared with the prevalence in the general Argentine population. As
a particular observation in our celiac population, the disease was rarely
associated with lymphocytic gastritis. We suggest that the chronic inflammatory
state evidenced by a gastric mucosal lymphocyte infiltration may be
secondary to the combination of H. pylori infection and chronic gluten
ingestion in gluten-sensitive subjects. |
| DIFFERENTIAL DIAGNOSIS |
KEY DIFFERENTIATING FEATURES |
| GENERAL |
|
-
Intraepithelial lymphocytosis in architecturally preserved proximal small intestinal mucosa: an increasing diagnostic problem with a wide differential diagnosis.
Brown I, Mino-Kenudson M,Deshpande V, Lauwers GY.
Sullivan Nicolaides Pathology, Taringa, Queensland, Australia.
|
-
Arch Pathol Lab Med. 2006 Jul;130(7):1020-5 Abstract quote.
CONTEXT: An increased intraepithelial lymphocyte density in an architecturally normal proximal small intestinal mucosal biopsy is a common finding facing surgical pathologists dealing with gastrointestinal biopsy specimens. Approximately 1% to 2% of all proximal small intestinal biopsies will show this change. It is increasingly recognized by surgical pathologists that gluten-sensitive enteropathy is an important cause of this pattern; however, gluten-sensitive enteropathy accounts for the minority of all cases. A wide variety of immunologic stimuli can raise intraepithelial lymphocyte numbers. Among the other common associations are enteric infection, autoimmune disease, drugs, and gastric Helicobacter infection.
OBJECTIVE: To outline the causes of intraepithelial lymphocytosis, to highlight the importance and the difficulties faced in establishing gluten-sensitive enteropathy as the cause, and to aid the surgical pathologist in the routine sign out of these cases.
DATA SOURCES: A review of the literature detailing the causes or associations of proximal small intestinal intraepithelial lymphocytosis is presented.
CONCLUSIONS: Increased lymphocyte numbers in the epithelium of architecturally preserved proximal small intestinal biopsies is a morphologic feature associated with a broad differential diagnosis.
|
Non–Gluten Sensitivity–Related Small Bowel Villous Flattening With Increased Intraepithelial Lymphocytes
Not All That Flattens Is Celiac Sprue
Neal S. Goldstein, MD
|
Am J Clin Pathol 2004;121:546-550 Abstract quote
Seven patients (mean age, 37.6 years; 5 women) had several weeks of gluten sensitivity (GS)-like symptoms; 2 had flu-like symptom prodromes.
The 7 cases had morphologically similar biopsy specimens; all tissue fragments had uniform injury—increased lymphoplasmacytic lamina propria inflammation, moderate to complete villous flattening, numerous crypt mitoses, and markedly increased villous intraepithelial lymphocytes (IELs).
All patients were diagnosed with GS and prescribed a gluten-free diet; all returned 9 to 38 weeks later questioning their diagnosis because symptoms had resolved substantially or completely. Clinical improvement was unrelated to gluten abstinence or ingestion. Repeated endoscopy and colonoscopy performed 4.1 to 16 months later showed normal mucosa in all 7 patients.
Diseases other than GS can cause marked villous flattening and increased villous IELs in adults. The cause of small bowel mucosal injury is unknown. A similar non-GS–associated clinicopathologic complex, assumed to be due to a protracted viral enteritis or slow regression of a virus-induced immune reaction, occurs in children.
The temporal aspects of symptom improvement and mucosal restitution in these 7 patients are similar to "acute self-limited colitis." An overly exuberant immune response to an infectious agent is possible. |
| OTHER |
|
| Autoimmune enteropathy |
Crypt injury and destruction
Anti-enterocyte antibodies |
| Tropical sprue |
No anti-endomysial antibodies
Response to antibiotic and folate therapy |
| Common variable immunodeficiency |
Paucity or absence of plasma cells
Marked lymphoid nodular hyperplasia
Giardia infection common |
| HELICOBACTER PYLORI GASTRITIS |
|
-
Duodenal intraepithelial lymphocytosis with normal villous architecture: common occurrence in H. pylori gastritis.
Memeo L, Jhang J, Hibshoosh H, Green PH, Rotterdam H, Bhagat G.
1Department of Pathology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA.
|
-
| Mod Pathol. 2005 Aug;18(8):1134-44. Abstract quote |
|
We have observed expansions of intraepithelial lymphocytes in duodenal biopsies from patients with Helicobacter pylori gastritis.
This study was undertaken to prospectively evaluate, unselected, paired gastric and duodenal biopsies from 50 patients with H. pylori gastritis and a comparison group of 30 patients with other types of gastritis (10 autoimmune and 20 reactive) to: (1) quantify duodenal intraepithelial lymphocytes, determine their distribution patterns, epithelial location, and phenotype, and (2) correlate the intraepithelial lymphocyte elevations with various features of gastric and duodenal pathology.
Intraepithelial lymphocytes were analyzed with antibodies including CD3, CD8, and TIA-1. A stain for H. pylori was performed on all gastric and duodenal biopsies. Duodenal intraepithelial lymphocytes from patients with H. pylori gastritis (using CD3) ranged from 3 to 42 lymphocytes/100 epithelial cells (mean 18.5) compared to 3 to 18 lymphocytes/100 epithelial cells (mean 6.6) in the comparison group.
Intraepithelial lymphocyte elevations were seen in 44% of the duodenal biopsies from patients with H. pylori gastritis (using CD3). Significant differences in the intraepithelial lymphocyte counts between patients with H. pylori gastritis and the comparison group were seen for all three T-cell antigens (P<0.001 for CD3 and CD8 and P<0.002 for TIA-1). Duodenal intraepithelial lymphocytes in the H. pylori+ cases had a latent cytotoxic phenotype, H. pylori was not visualized in any of the duodenal biopsies from patients with H. pylori gastritis, and no patient had clinical evidence of celiac disease.
Our study highlights frequent duodenal intraepithelial lymphocytosis in individuals with H. pylori gastritis and the lymphocyte distribution patterns (and numbers) overlapped with those described for celiac disease patients. H. pylori gastritis must be considered as a possible explanation for duodenal intraepithelial lymphocytosis with normal villous architecture, especially when lymphocytosis is patchy, intraepithelial lymphocytes display a 'latent' cytotoxic phenotype, and the clinical findings and serologic profile does not fit celiac disease.
|
| Infectious enteritis-usually viral |
Normal IEL counts |
| Food protein intolerance (eggs, cow milk) |
Increased eosinophils
Allergic manifestations like atopy
Response to elimination diets |
| PROGNOSIS AND TREATMENT |
CHARACTERIZATION |
| PROGNOSIS |
|
| Modified Marsh Classification |
See below |
|
Increased risk of esophageal squamous cell carcinoma
|
|
|
Increased risk of small bowel adenocarcinoma
|
|
|
|
|
|
Refractory sprue syndrome with clonal intraepithelial lymphocytes
evolving into overt enteropathy-type intestinal T-cell lymphoma.
Daum S, Hummel M, Weiss D, Peters M, Wiedenmann B, Schaper F, Stein
H, Riecken EO, Foss H.
Department of Gastroenterology and Infectious Diseases, Klinikum
Benjamin Franklin, Free University of Berlin, Berlin, Germany.
|
Digestion 2000;62(1):60-5 Abstract quote
INTRODUCTION: Recently, patients with refractory sprue have been shown
to contain a clonal proliferation of phenotypically abnormal intraepithelial
lymphocytes in their intestine. Whether this signifies early enteropathy-type
intestinal T-cell lymphoma (EITCL) or a reactive condition is not clear.
We report on a patient presenting with the findings of refractory sprue
who subsequently developed overt EITCL.
MATERIAL AND METHODS: Duodenal biopsies from 1997 (refractory sprue)
and duodenal and jejunal biopsies from 1998 (intestinal T-cell lymphoma)
were compared by immunohistochemistry and PCR for the detection of T-cell
receptor (TCR)-gamma gene rearrangements. Clonal PCR products were sequenced.
RESULTS: The duodenal biopsies from both 1997 and 1998 and the jejunal
tumor biopsy showed villus atrophy and an increase of intraepithelial
lymphocytes with an abnormal immunophenotype (CD3+, CD4-, CD8- and TCR-beta-).
In all duodenal specimens including the one from 1997, and the jenunal
tumor biopsy, an identical clonal amplificate was detected by enzymatic
amplification of the TCR-gamma gene.
CONCLUSION: These data suggest that refractory sprue containing a clonal
proliferation of phenotypically abnormal intraepithelial lymphocytes
may represent an early manifestation of EITCL. The detection of immunohistochemical
negativity for several antigens normally found on intraepithelial lymphocytes
such as CD8 or the TCR-beta chain in combination with clonal T-cell
populations by PCR may be helpful in identifying refractory sprue with
a malignant transformation.
|
|
Refractory sprue, coeliac disease, and enteropathy-associated T-cell
lymphoma. French Coeliac Disease Study Group.
Cellier C, Delabesse E, Helmer C, Patey N, Matuchansky C, Jabri
B, Macintyre E, Cerf-Bensussan N, Brousse N.
Department of Gastroenterology, Hopital Laennec, INSERM E9925, Paris,
France.
|
Lancet 2000 Jul 15;356(9225):203-8 Abstract quote
BACKGROUND: Adult refractory sprue is a poorly defined disorder. We
did a multicentre national study of patients with refractory sprue to
characterise their clinical and pathological profile and outcome, and
to assess the frequency and prognostic significance of phenotypic and
molecular abnormalities in the intraepithelial T-cell population.
METHODS: Patients with severe symptomatic villous atrophy mimicking
coeliac disease but refractory to a strict gluten-free diet, and with
no initial evidence of overt lymphoma, were diagnosed at gastrointestinal
referral centres between 1974 and 1998. Fixed and/or frozen duodenojejunal
biopsy samples were reanalysed and immunostained with CD3 and CD8 monoclonal
antibodies to find out the phenotype of intraepithelial lymphocytes
(IEL). TCRgamma gene rearrangements were assessed on frozen biopsy samples
by multiplex fluorescent PCR.
FINDINGS: There were 21 patients with refractory sprue and 20 controls
with coeliacs disease. 16 (84%) of 19 assessed patients had an aberrant
intraepithelial lymphoid intestinal population expressing intracytoplasmic
CD3 but not surface CD8. Clonal intestinal TCRgamma gene rearrangements
were found in 13 (76%) of 17 patients assessed; four (out of 12 assessed)
had clonal dissemination to the blood. The 16 patients with an aberrant
phenotype all had uncontrolled malabsorption; three subsequently developed
overt T-cell lymphoma, and eight died. The three (16%) patients without
aberrant clonal IEL made a complete clinical and histological recovery
with steroid therapy plus a gluten-free diet.
INTERPRETATION: An immunophenotypically aberrant clonal intraepithelial
T-cell population (similar to that of most cases of enteropathy-associated
T-cell lymphoma) can be found in up to 75% of patients with refractory
coeliac sprue; its identification by simple diagnostic techniques represents
a marker of poor outcome (including occurrence of overt T-cell lymphoma).
We suggest that refractory sprue associated with an aberrant clonal
IEL may be the missing link between coeliac disease and T-cell lymphoma
and may be classified as cryptic enteropathy-associated T-cell lymphoma.
|
|
Risk of Non-Hodgkin Lymphoma in Celiac Disease
Carlo Catassi, MD; Elisabetta Fabiani, MD; Giovanni Corrao, PhD; Maria
Barbato, MD; Amalia De Renzo, MD; Angelo M. Carella, MD; Armando Gabrielli,
MD; Pietro Leoni, MD; Antonio Carroccio, MD; Mariella Baldassarre, MD;
Paolo Bertolani, MD; Paola Caramaschi, MD; Michele Sozzi, MD; Graziella
Guariso, MD; Umberto Volta, MD; Gino R. Corazza, MD; for the Italian
Working Group on Coeliac Disease and Non–Hodgkin's-Lymphoma
|
JAMA. 2002;287:1413-1419 Abstract quote
Context
Celiac disease is one of the most common lifelong disorders. Non-Hodgkin
lymphoma is a possible complication of celiac disease and may lead to
a large portion of lymphoma cases.
Objective
To quantify the risk for developing non-Hodgkin lymphoma of any primary
site associated with celiac disease.
Design and Setting
Multicenter, case-control study conducted between January 1996 and December
1999 throughout Italy.
Patients
Cases were older than 20 years (median, 57; range, 20-92 years) with
non-Hodgkin lymphoma of any primary site and histological type and were
recruited at the time of the diagnosis. Controls were healthy adults
(2739 men and 2981 women) from the general population.
Main Outcome Measure
Positive test result for class A serum antiendomysial antibody.
Results
Celiac disease was diagnosed in 6 (0.92%) of 653 patients with lymphoma.
Of the 6 cases, 3 were of B-cell and 3 were of T-cell origin. Four of
6 cases had lymphoma primarily located in the gut. In the control group,
24 (0.42%) had celiac disease. The odds ratio (adjusted for age and
sex) for non-Hodgkin lymphoma of any primary site associated with celiac
disease was 3.1 (95% confidence interval [CI], 1.3-7.6), 16.9 (95% CI,
7.4-38.7) for gut lymphoma, and 19.2 (95% CI, 7.9-46.6) for T-cell lymphoma,
respectively. The risk for non-Hodgkin lymphoma for the overall population,
which was adjusted for age and sex, was 0.63% (95% CI, - 0.12% to 1.37%).
Conclusion
Celiac disease is associated with an increased risk for non-Hodgkin
lymphoma, especially of T-cell type and primarily localized in the gut.
However, the association does not represent a great enough risk to justify
early mass screening for celiac disease.
|
| TREATMENT |
Gluten free diet |
-
Risk of celiac disease autoimmunity and timing of gluten introduction in the diet of infants at increased risk of disease.
Norris JM, Barriga K, Hoffenberg EJ, Taki I, Miao D, Haas JE, Emery LM, Sokol RJ, Erlich HA, Eisenbarth GS, Rewers M.
Department of Preventive Medicine and Biometrics, University of Colorado at Denver and Health Sciences Center, Denver, CO 80262, USA.
|
-
| JAMA. 2005 May 18;293(19):2343-51. Abstract quote |
|
CONTEXT: While gluten ingestion is responsible for the signs and symptoms of celiac disease, it is not known what factors are associated with initial appearance of the disease.
OBJECTIVE: To examine whether the timing of gluten exposure in the infant diet was associated with the development of celiac disease autoimmunity (CDA).
DESIGN, SETTING, AND PATIENTS: Prospective observational study conducted in Denver, Colo, from 1994-2004 of 1560 children at increased risk for celiac disease or type 1 diabetes, as defined by possession of either HLA-DR3 or DR4 alleles, or having a first-degree relative with type 1 diabetes. The mean follow-up was 4.8 years.
MAIN OUTCOME MEASURE: Risk of CDA defined as being positive for tissue transglutaminase (tTG) autoantibody on 2 or more consecutive visits or being positive for tTG once and having a positive small bowel biopsy for celiac disease, by timing of introduction of gluten-containing foods into the diet.
RESULTS: Fifty-one children developed CDA. Findings adjusted for HLA-DR3 status indicated that children exposed to foods containing wheat, barley, or rye (gluten-containing foods) in the first 3 months of life (3 [6%] CDA positive vs 40 [3%] CDA negative) had a 5-fold increased risk of CDA compared with children exposed to gluten-containing foods at 4 to 6 months (12 [23%] CDA positive vs 574 [38%] CDA negative) (hazard ratio [HR], 5.17; 95% confidence interval [CI], 1.44-18.57). Children not exposed to gluten until the seventh month or later (36 [71%] CDA positive vs 895 [59%] CDA negative) had a marginally increased risk of CDA compared with those exposed at 4 to 6 months (HR, 1.87; 95% CI, 0.97-3.60). After restricting our case group to only the 25 CDA-positive children who had biopsy-diagnosed celiac disease, initial exposure to wheat, barley, or rye in the first 3 months (3 [12%] CDA positive vs 40 [3%] CDA negative) or in the seventh month or later (19 [76%] CDA positive vs 912 [59%] CDA negative) significantly increased risk of CDA compared with exposure at 4 to 6 months (3 [12%] CDA positive vs 583 [38%] CDA negative) (HR, 22.97; 95% CI, 4.55-115.93; P = .001; and HR, 3.98; 95% CI, 1.18-13.46; P = .04, respectively).
CONCLUSION: Timing of introduction of gluten into the infant diet is associated with the appearance of CDA in children at increased risk for the disease.
|
|
Refractory coeliac disease: a window between coeliac disease and
enteropathy associated T cell lymphoma.
Mulder CJ, Wahab PJ, Moshaver B, Meijer JW.
Depts. of Gastroenterology and Pathology, Rijnstate Hospital, P.O.
Box 5555, 6800 TA Arnhem, The Netherlands
|
Scand J Gastroenterol Suppl 2000;(232):32-7 Abstract quote
The treatment of coeliac disease (CD) is straightforward and simple:
life-long adherence to a gluten-free diet. However, in a small subgroup
of patients, the clinical and histological abnormalities persist or
recur. This non-responsiveness leaves a poorly understood syndrome known
as refractory coeliac disease (RCD). A specific definition of RCD is
lacking in the literature.
We speculate that RCD may appear in a subgroup of coeliacs with persisting
histologic abnormalities. In all patients screened for RCD we look for
DQ2 and DQ8. In non-DQ2/DQ8 patients we reconsider the diagnosis of
CD and of auto-immune enteropathy. Most of the patients referred to
us because of suspicion of RCD are affected by other diseases. Probably
the commonest cause of non-responsiveness is continued gluten intake.
Exocrine pancreas insufficiency, hyperthyroid disease, collagenous colitis
are other common explanations. RCD and enteropathy-associated T cell
lymphomas (EATL) can be distinguished by intra-epithelial lymphocyte
phenotyping and TCR-gamma gene rearrangements.
In RCD, an unexplained sustained stimulation of T cell cytotoxic activity
is present. Immunosuppressive treatment might moderate this. Cyclosporine
has been reported as a resounding success in case reports; however,
our results were disappointing. We suggest azathioprine and steroids
in RCD without aberrant T-lymphocytes in their mucosa. However, in RCD
with aberrant T-lymphocytes we suggest chemotherapy. As the prognosis
of EATLs is extremely poor the early detection of RCD with aberrant
T cells is crucial.
|
