GUIDELINES FOR THE MANAGEMENT OF PATIENTS WITH

COELIAC DISEASE
SUMMARY
Coeliac disease is a life-long inflammatory condition of the gastrointestinal tract that affects the small intestine
in genetically susceptible individuals. A small intestinal biopsy is mandatory to confirm the diagnosis.
Treatment involves a strict gluten-free diet that excludes wheat, rye and barley which should be supervised by a
dietician. The role of oats is controversial. Follow-up is important because of potential long-term
complications.
INTRODUCTION
Definition: Coeliac disease (C! may be defined as an inflammatory condition of the small intestinal mucosa,
that is most mar"ed proximally, and which improves morphologically when gluten is removed from the diet.
The disorder may alternatively be termed gluten-sensitive enteropathy or non-tropical sprue. #ecent evidence
suggests C has a $% prevalence of &'())* approximately &+) patients at any one time are cared for in an
average istrict ,eneral -ospital. There is considerable under-recognition of the condition which increased
use of serological screening should correct. This particularly applies in patients presenting to ,eneral
.ractitioners with either lethargy, anaemia or symptoms of irritable bowel syndrome. ermatitis herpetiformis
(-! is a related disorder in which there is an itchy blistering s"in eruption that fre/uently affects the "nees,
elbows, buttoc"s and bac". Confirmation of a diagnosis of - includes the finding of granular 0gA at the
dermo-epidermal 1unction of uninvolved s"in on biopsy. The ma1ority of patients with - have a small
intestinal enteropathy that improves with gluten withdrawal.
C presents at all ages with protean manifestations. .atients may present with clinical or haematological
features, or may be identified by serological screening of asymptomatic relatives.
SYMPTOMS
(a) Chi!: 2ymptoms in children may occur following weaning with presentation between 34&5 and ( years.
They comprise failure to thrive, diarrhoea, irritability and anorexia. Children also present over the age of (
with short stature, anaemia of during wor"up following a diagnosis of diabetes mellitus.
Mo!e" of #$e"entation
Classical presentation aged 9-24 months - There is gradual failure to gain weight or loss of weight after
introduction of cereals, the child having been previously well. This is accompanied by anorexia and
alteration in stools which are softer, paler, larger and more fre/uent than usual. There may be
abdominal distension, muscle wasting and hypotonia.
5
Presentation in infants before 9 months - 6omiting is fre/uent and may be pro1ectile in this age group.
iarrhoea may be severe, especially with intercurrent infections, not necessarily gastroenteritis.
Abdominal distension may occur. 0t is difficult to distinguish from the post-enteritis4cow7s mil"
sensitive enteropathy syndrome.
Presentation with constipation - These children can be hypotonic with mar"ed abdominal distension.
This is an uncommon presentation.
Presentation at older age - 2hort stature, iron-resistant anaemia, ric"ets and personality problems all
may occur. iarrhoea is not a prominent feature. 2uch a mode of presentation is characteristic for
children in 8ritain originating from the northern part of the 0ndian sub-continent. .resentation may be
with symptoms compatible with a diagnosis of irritable bowel syndrome or recurrent mouth ulcers.
Presentation in asymptomatic siblings - Following a case of coeliac disease having been positively
diagnosed, siblings should have clinical history and growth chec"ed. 2hould a suspicion of coeliac
disease arise then 0gA transglutaminase or endomysial antibodies and either 0g, gliadin or tTg
antibodies should be measured. The latter is re/uired to screen for the 59 of patients with coeliac
disease who have 0gA deficiency. A small intestinal biopsy should then be performed if there is a raised
titre of one of the above circulating antibodies.
(%) A!&t: The symptomatology in adults is often less acute. The pea" incidence of diagnosis in adults is in
the third decade with a further smaller one in the fifth and sixth decades.
:)-3)9 have general lassitude.
;+-:)9 have diarrhoea.
:+9 have asymptomatic iron4folate deficiency.
&+-()9 have vitamin deficiency.
&)9 have vitamin % deficiency.
There are rarer problems, incuding reduced fertility, psychological disturbances or neurological deficit resulting
in ataxia . There is often a delay of several years before the diagnosis is made.
(
IN'ESTIGATION
I( Dia)no"ti* Te"t"
(a) Inte"tina +io#",: iagnosis re/uires a small intestinal biopsy, the current usual practice being for
endoscopic biopsies to be ta"en from the distal duodenum. 2hould there be any doubt, endoscopic biopsies
should be repeated or, preferably, a 1e1unal biopsy should be underta"en using a suction peroral biopsy capsule,
or a small bowel enteroscope.
The characteristic histological changes in a small intestinal biopsy are loss of height, crypt hyperplasia, a
chronic inflammatory cell infiltrate of the lamina propria, lymphocytic infiltration of the epithelium, and a
decrease in the epithelial surface-cell height. Confusion can occur when these changes are only mild,
particularly when only one endoscopic duodenal biopsy is histologically assessed and when this has been cut
tangentially. A follow-up biopsy should be obtained < to = months after starting treatment with a gluten-free
diet (,F!, at which time there should have been an improvement in the small intestinal morphology. efinite
cases do occur however where only mild histological changes are present.
These criteria in practice do not need to be fulfilled in every case diagnosed as coeliac disease except in two
particular situations' (i! a child previously diagnosed as suffering from coeliac disease and having a gluten-free
diet should be reinvestigated in order to fulfil these criteria if there is any doubt about the original diagnosis,
particularly if the child was started on such a diet without a previous small intestinal biopsy* (ii! if the child
was less than 5 years of age at the time of diagnosis. 0t must be appreciated that although a flat small intestinal
mucosa is characteristic of coeliac disease, there are other causes of such a mucosa. 0f the diagnosis is still in
doubt, it is mandatory to ta"e an additional small intestinal 1e1unal biopsy after a formal gluten challenge. This
should comprise at least &)g of gluten, that is contained in four slices of normal bread, per day for a minimum
of 5 wee"s, although this may need to be much longer, and = wee"s in the case of children. 0f the patient
experiences severe symptoms on gluten challenge, the date of the biopsy should be brought forward. The
development of symptoms on gluten challenge without evidence of an abnormal small intestinal biopsy is
insufficient to ma"e the diagnosis.
0t is now considered acceptable to ta"e only an initial biopsy in patients who have typical histological features,
as long as they have positive antibodies to gliadin and endomysium and experience symptomatic remission on
withdrawal of dietary gluten. The diagnosis is more secure, however, if a second biospy is ta"en which shows
histological improvement following gluten withdrawal.
(%) Anti%o!, St&!ie": 2erological screening tests can be performed for antibodies to tT,, gliadin and
endomysium. 0g, and 0gA anti-tT, antibodies can be measured easily and cheaply, using >?02A techni/ues.
They are highly sensitive mar"ers, being present in 3)9 of patients with untreated disease, and are relatively
specific. They are most useful as a preliminary step in screening or to monitor the condition as levels tend to
fall after treatment with a ,F (0a!.
<
II( S&##o$ti-e In-e"ti)ation"
A number of routine blood tests should be carried out to identify nutritional deficiencies including
haemoglobin, 8&5, folate, iron, serum albumin, and calcium. These should be measured at diagnosis, during
symptomatic relapse, and during pregnancy. 0t is also reasonable to perform these routinely at annual follow-
up. Tests of malabsorption can be used to assess severity of disease in con1unction with mucosal histology (see
advice document on malabsorption!( 2mall intestinal barium studies may be used to exclude other causes of
malabsorption and diarrhoea, and for diagnosing complications of C, such as strictures and small bowel
lymphoma.
TREATMENT
I( Dieta$, T$eat.ent
(a) G&ten E/*&"ion: The cornerstone of therapy is adherence to a gluten free diet (,F!. This means the
exclusion of foods containing wheat, rye, barley and oats, although the toxicity of oats is still debated. The
avoidance of these cereals is a formidable tas" as they are found in bread, biscuits, ca"es, pastries, brea"fast
cereals, pasta, beer, and most soups, sauces and puddings (@al"er-2mith et al, &33)!.
>vidence suggests (Aantuinen et al, &33+! that oats are not harmful to individuals with coeliac disease.
-owever, it should be remembered that the ma1ority of commercially available oat flour is contaminated with
&)-&+9 wheat.
.atients may supplement their diet with commercial gluten-free products that are available on prescription by
general practitioners and include gluten-free flour, bread, biscuits, and pasta. .rescriptions should be on F.&)
forms clearly mar"ed AC82, an abbreviation for Baccording to the borderline substance actB. Cany gluten-free
flours and bread mixes are based on purified wheat starch from which most gluten proteins have been removed.
Cost patients with coeliac disease tolerate these products well, although a minority cannot. These individuals
should be advised to ta"e a strict ,F for which they ingest only commercial non-wheat starch based gluten-
free products.
2eventy per cent of adults, and a greater proportion of children, respond promptly to a ,F, showing
improvement of symptoms within wee"s or days. -istological improvement usually ta"es many months to
occur.
(%) Tota -" Pa$tia G&ten E/*&"ion: The ris" of developing small intestinal lymphoma is increased in
patients with C who ingest a diet that contains gluten. Dutritional deficiencies are also more li"ely to occur.
0t has been shown that early introduction of a gluten-free diet decreases the subse/uent ris" of developing
autoimmune disorders, particularly diabetes mellitus. 0t therefore seems reasonable to recomend a strict ,F,
even if patients are asymptomatic on a low gluten inta"e (000!. ,ood dietary compliance should reduce the ris"
of osteoporosis in later life.
+
(*) Nee! Fo$ Life0Lon) T$eat.ent: Adolescents may stop their diet in the mista"en belief that they have
Bgrown out ofB their C. 2hould the diagnosis be in any doubt, a gluten challenge and repeat 1e1unal biopsy
should be underta"en* if the diagnosis is established life-long treatment should be recommended.
(!) Dieta$, S&##e.ent": Cany patients will be found to be suffering from dietary deficiencies at the time of
diagnosis, the commonest being iron, folic acid, calcium and vitamin 8&5. Although these usually resolve
spontaneously once on a ,F, it seems reasonable to ensure rapid correction with appropriate supplements.
(e) +one A%no$.aitie": Cany individuals have osteopenia. 0t is usual practice to consider bone densitometry
scanning on presentation which may be repeated after one to two years of dietary therapy if the initial value is
low. Esteoprosis in post-menopausal women may warrant hormone replacement therapy and the use of
bisphosphonates in some individuals. Calcium supplementation to achieve an inta"e of &+))mg a day may be
considered.
(f) H,#o"#eni".: .atients with coeliac disease invariably have a degree of hyposplenism for which
immunisation with pneumococcal vaccine may be underta"en.
()) Info$.ation an! S&##o$t: As mentioned above, adherence to a ,F is not easy, even in ideal
circumstances. For individual patients this tas" can be complicated by family and professional commitments,
as well as peer pressure. Adolescence is often a particularly difficult time, when young patients may feel
excluded from their peer group by their dietary restriction. The value of careful explanation and
encouragement cannot be overemphasised, and the need for supervision by a dietitian is mandatory. @ritten
advice should be provided whenever possible, and all patients should be encouraged to 1oin the $% Coeliac
2ociety.
II( Foo10U#
0n patients with a satisfactory response to diet, specialist outpatient follow-up should ideally be at six to twelve
month intervals to assess symptomatic improvement, nutritional state, dietary compliance, and to chec" routine
blood tests. A chec" small intestinal biopsy four to six months after initiating treatment should be performed
when improvement in the small intestinal villous architecture is expected. 0n some hospitals follow up may be
1oint with the patientFs general practitioner. .atients should be referred bac" to a consultant clinic if there are
any abnormalities in the blood tests underta"en.
0t is important to review patients at times of stress, whether this be physical or emotional. .regnancy is a
particularly important time which may lead to a deterioration in symptoms, or asymptomatic nutritional
deficiencies. ?ow levels of folic acid have been associated with miscarriage and foetal neural tube defects, and
so should be carefully monitored. .atients who are contemplating conception should supplement their diet with
folic acid as they are prone to folic acid deficiency,
=
8ecause of the possible long term complications of disease, such as lymphoma and bone disease, it is strongly
recommended that life-long follow-up be maintained. The general practitioner should be aware of potential
complications and re/uest specialist review if re/uired.
III( Mana)e.ent Of Poo$ Re"#on"e An! Rea#"e
The assessment of patients who fail to respond to diet involves three steps' (a! assess dietary compliance, (b!
confirm the diagnosis, and (c! exclude other coincident disease. The management of patients who relapse after
initial recovery is broadly similar, although more emphasis is given to exclusion of coincident disease,
including complications such as lymphoma.
(a) Dieta$, Co.#ian*e: Careful /uestioning will identify most patients who are, "nowingly or un"nowingly,
ta"ing dietary gluten. Eccasionally, very diligent patients continue to have symptoms due to very small
amounts of ingested gluten, and the dietary history needs to be very detailed. 0n some cases identification of the
source of dietary gluten may only be possible by admitting the patient to hospital, when the patient can be
restricted to a supervised and carefully prepared ,F.
(%) Confi$.ation Of The Dia)no"i": This re/uires review of the original histology and associated clinical
information. 0f there is any doubt, a repeat biopsy should be underta"en. ,luten challenge may be necessary,
and if they have not already been performed, antibody studies can help to strengthen the diagnosis.
(*) Othe$ Coin*i!ent Di"ea"e: 0solated persistent symptoms should be investigated as in a patient without C.
Ebviously, the most appropriate investigations will depend on the individual case. .articular attention should
be paid to conditions which, though rare in the general population, occur more fre/uently in association with
C, including lactose intolerance.
(!) I..&no"&##$e""ion: Coeliac disease can be controlled with systemic corticosteroids, with rapid cessation
of diarrhoea, weight gain, and improvement in fat absorption. -owever, within a few days of stopping
treatment there is usually a deterioration. 0n general, they are best avoided, and with careful diagnosis and
dietary assessment they rarely need to be used.
I'( Mana)e.ent Of Co.#i*ation" An! A""o*iate! Con!ition"
(a) De$.atiti" He$#etifo$.i": ermatitis herpetiformis complicates 5-+9 of cases of gluten-sensitive
enteropathy, and the ma1ority cases of - exhibit a degree of gluten-sensitive enteropathy.
apsone is the drug of choice for the condition, although it does have significant side-effects. .atients should
ta"e a strict ,F, as this results in a significant improvement after six to twelve months and permits a
reduction in the dose of, or elimination of the need for, dapsone. A few individuals are unable to tolerate
dapsone because of side effects, which include a dose-dependent haemolytic anaemia, methaemoglobinaemia,
and headache. These patients can alternatively be treated with sulphapyridine.
;
(%) Mai)nan*,: (i! Lymphoma: The mechanism by which C predisposes to lymphoma is un"nown, though
the association is not doubted. The commonest presentation involves the return of symptoms of diarrhoea,
associated with both weight loss and lassitude in a patient with established coeliac disease. 2tandard
investigations, including 1e1unal biopsy and small bowel barium studies, are li"ely to have a low yield, even
when the lymphoma is suspected, because of the associated subtotal villous atrophy. The histological
appearance of peripheral lymph nodes, the liver or bone marrow may be diagnostic, and ultrasound, computer
aided tomography, or nuclear magnetic resonance scanning may be useful. 2mall bowel enteroscopy may be of
help by allowing direct visualisation and biopsy of a greater proportion of the small intestine. ?aparotomy or
laparoscopy, with lymph node, liver, and full-thic"ness intestinal biopsies is a useful diagnostic tool, and often
the only way to achieve a definitive diagnosis. Treatment is difficult and usually involves surgery, radiotherapy
and chemotherapy (ii! There is an increased ris" of small bowel adenocarcinoma. 0t often presents with non-
specific symptoms and there is often a significant delay in diagnosis. As a result, the patient often has
metastatic disease with poor prognosis. 2urgery with consideration of chemotherapy is the mainstay of
treatment. There is also an increased prevalence of carcinoma of the colon and oesophagus.
(*) U*e$ati-e 2e3&no0ieiti": This is an unusual complication in which unresponsive C is associated with
ulceration and stricturing. .atients may become very unwell and are often unresponsive to medical therapy.
The discrimination between this and lymphoma can normally only be made at surgery, and in some instances
lymphoma seems to have developed on a bac"round of 1e1uno-ileitis. .atients should be advised to continue
with a gluten-free diet, but early surgery is indicated if there is no resolution of symptoms.
(!) Mi*$o"*o#i* Coiti": A minority of patients experience concomitant colitis which in some cases may be
microscopic or lymphocytic. Appropriate therapy should be given involving the use of mesalaGine, peptobismol
or, in resistant cases, low dose systemic steroids.
Othe$ Co.#i*ation": A ,F is low in fibre and may exacerbate constipation or symptoms of irritable bowel
syndrome. Carbohydrate intolerance and small bowel bacterial overgrowth may also occur, and there is an
increased prevalence of diabetes mellitus. 0nfertility is common in untreated patients. #arely neurological
complications may occur. There is evidence that many coeliac patients suffer from osteoporosis in later life
(000!.
:
ADDITIONAL INFORMATION
S*he!&e fo$ G&i!eine" Re-ie1 This is an interim document which is being produced while the evidence
base is being added. 0t is proposed to review these guidelines bi-annually.
The Coeia* So*iet, of the U4, .E 8ox 55), -igh @ycombe, 8uc"s, -.&& 5-H
Tel' )&<3< <(;5;: Fax' )&<3< <;<(<3
S&))e"te! Rea!in):
Ciclitira .A,%ing A? and Fraser A I5))&J A,A. Cedical position statement and technical review on celiac
sprue. ,astroenterology &5)* &+5-&+<.
Ciclitira .A Celiac sprue and related problems. 0n' Current Therapy in Gastroenterology and Lier !isease.
(ed! 8ayless TC. Cosby Hear 8oo", .hiladelphia $2A, &33<, =:, 53:-()(
3
-agman 8 (ed! The gluten-free gourmet' living without wheat. (&33)! and Core from the gluten-free
gourmet. (&33(!. 8oth from -enry -olt and Company, Dew Hor"
-olmes ,%T, .rior ., ?ane C#, .ope #D K Allen #D (&3:3! Calignancy in coeliac disease-effect of a
gluten-free diet. Gut 567 (((-((:
-owdle . (ed! Coeliac isease. 8aillieres Clinical ,astroenterology. &33+
Aanatuinen >%, .i""arainen .-, %emppainen TA, %osma 6>, Aarvinen #C%, $usitupa C0A K Aul"unen #A%
(&33+! A comparison of diets with and without oats in adults with coeliac disease. "ew #ngland $ournal of
%edicine 5557 &)((-&)(;
Carsh CD (ed! Coeliac isease. 8lac"well 2cientific .ublications. &335
@al"er-2mith AA, ,uandalini 2, 2chmitG A, 2chmerling C K 6isa"orpi A% (&33)! #evised criteria for
diagnosis of coeliac disease. &rchies of !isease in Childhood 887 :3&-:3<
S&##ie$" of G&ten0f$ee P$o!&*t":
Cantassium, 55+-553 .utney 8ridge #oad, ?ondon, 2@&+ 5.H (Tel' )&:& :;< &&()! (Trufree products!
Croo"es -ealthcare, .E 8ox +;, Central .ar", ?enton ?ane, Dottingham, D,; 5?A (Tel' )&&+ 3+) ;<(&!
Food @atch, 8utts .ond 0ndustrial >state, 2turminster Dewton, orset, T&) &AL (Tel' )&:5 ((5 +)5(!
,eneral esigns ?td, .E 8ox (:, %ingston upon Thames, 2urrey, %T5 ;H. (Tel' )&:& ((= 5(5(! (>ner-, and
.astariso .roducts!
,luten Free Foods ?td, : Mueen Anne 2treet, ?ondon, @&C 3? (Tel' )&:& 3+< ;(<:! (8ar"at products!
-A -einG, -ayes .ar", -ayes >nd #oad, -ayes, Ciddx, $8< :-? (Tel' )&:& +;( ;;+;!
Aacob7s 8a"ery ?td, 2uttons 8usiness .ar", >arley, #eading, #,= &AL (Tel' )&;( <<3 5)))! (?iga products!
%allo Foods ?imited, 2unbury on Thames, T@&= ;A2 (Tel' )&3( 5(+ +()(! (%allo products!
?ar"hall ,reen Farm ?td, 55+ .utney 8ridge #oad, ?ondon, 2@&+ 5.H (Tel' )&:& :;< &&()!
The Custard 2hop, ( 8ridewell Alley, Dorwich, D#5 &AM (,enuine Custard, coded ,2F! (Tel' )&=) (=5
;::3!
Cilupa, Cilupa -ouse, $xbridge #oad, -illingdon, $xbridge, Ciddx $8&) )D> (Tel' )&:& +;( 33==!
(.re1omin products!
Dutricia ietary .roducts ?td, Dewmar"et Avenue, @hite -orse 8usiness .ar", Trowbridge, @ilts, 8A&< )NM
(Tel' )&55+ ;=:(:&! (Fax' )&55+ ;=: :<;! (,lutenex 8iscuits, ,F ietary, ,lutafin, ?oprofin, #ite iet
.roducts!
2cientific -ospital 2upplies ?td, &)) @avertree 8oulevard, @avertree Technology .ar", ?iverpool, ?; 3.T
(Tel' )&+& 55: &335! (Auvela, ?ifestyle .roducts!
$ltrapharm ?td, .E 8ox &:, -enley on Thames, Exon, #,3 &A@ (Tel' )&<3& +;:)&=! (Aproten, Arnott7s
#ice Coo"ies, 8i-aglut, .olial, 2char, $ltra products!