1

MINISTRY OF HEALTH OF UKRAINE

NATIONAL BOGOMOLETS MEDICAL UNIVERSITY

“Approved”
at methodical meeting
of the pediatric department № 1

The head of the department

Berezenko V.S.
“______” _____________ 2021

METHODIC GUIDELINES
for students self-training during preparation to the practical class

Discipline Pediatrics
Модуль № 1
Module 1

Topic Differential diagnostics of functional and organic

diseases of stomach and intestines in children.
Complication of the ulcer
Course 6
Faculty Medical № 1

Кyiv-2019
 2

1 Actuality of the topic. The digestive system (DS) functional and organic disorders occupy
second place at a structure of all diseases of the childhood. The most spread among them are
functional intestinal disorders and gastritis. The rate of ulcer in children has been decreased
during last years and now makes 1.7 – 6.0% according to data of different authors.
“Rejuvenation” of digestive diseases and atypical forms development requiring more thorough
differential diagnostics and prevention of possible complications is marked last years

2. Certain aims:

1. To study analyzing the reasons and factors contributing to digestive diseases development in
children;

2. To be able to explain main ling of pathogenesis of these diseases

3. To interpret found symptoms and syndromes and laboratory and instrumental investigations
results.

4. To study differential diagnostics of intestinal functional and organic diseases by their clinical-
and-laboratory and instrumental signs.

5. To study making the diagnosis according the classification.

6. To be able to evaluate ulcer’s symptoms and provide the emergency in its complications in the
child

7. To study composing treatment plan and rehabilitation measures in functional and organic
intestinal diseases

3. Basic knowledge:
Previous disciplines Mastered skills

1. Normal anatomy Anatomic features of stomach and intestines

2. Normal physiology Digestion physiology, mechanisms of gut’s
functioning regulation
3. Biology and genetics Importance of genetic factors for child’s
growth and maturation
4. Hystology Hystology of stomach and intestines
5. Pathologic physiology Peculiarities of typical pathological processes
in the digestive system diseases
6. Pharmacology Groups of drugs used in digestive diseases
treatment and the mechanism of their action
7. Main principles of nursing Peculiarities of feeding of children of different
age with digestive problems
8.Propedeutic therapy and pediatry Gut inspection methodic and evaluation of
main laboratory and instrumental data
9. Psychology Application of childhood’s psychology while
working with a child
10. Radiology Interpretation of the intestinal X-rays
 3
4. Tasks for self-training during preparation to the class
4.1. Main terms for the topic
Тerm Definition
Malabsorption Complex of symptoms resulted by disorders of absorption processes in small
syndrome intestines and manifests in diarrhea and metabolic disorders
Irritable Pathological condition related to intestinal motility disorders without
bowel structural changes of digestive organs’ mucosa
syndrome
Duodenal and Chronic exacerbating tending to progressing and complicated course
stomach ulcer inherited disease of the child manifested in ulceration of either duodenal or
stomach’s mucosa

4.2. Theoretical questions for the class

1. Etiological factors leading in malabsorption syndrome development
2. Etiological factors leading in irritable bowel syndrome development
3. Etiological factors leading in stomach and duodenal ulcer development
4. Main links of malabsorption pathogenesis
5. Main links of irritable bowel syndrome pathogenesis
6. Main links of duodenal and stomach ulcer pathogenesis
7. Clinical peculiarities of the intestinal diseases in children of different age
8. Laboratory and instrumental methods of the intestinal diseases diagnostics
9. Principles of the intestinal diseases treatment

4.3. Практичні завдання, які виконуються на занятті:

1. Участь у демонстрації хворого викладачем.
2. Самостійна курація хворого.
3. Складання плану обстеження.
4. Диференціальна діагностика, оцінка результатів лабораторно-інструментальних
досліджень.
5. Складання плану лікування.
6. Засвоєння практичних навичок із надання допомоги при виникненні невідкладних
станів при захворюваннях ШКТ
7. Оформлення результатів практичної роботи.

5. Contents

Recurrent abdomіnal paіn (RAP) іn chіldren was defіned and іdentіfіed because іt was
recognіsed that іt was very common, very dіsruptіve to famіlіes and often not accompanіed by
easіly defіnable organіc pathology. Іt іs a condіtіon comprіsіng both organіc and functіonal
dіsorders and іs therefore clіnіcally challengіng to dіagnose and treat.
Chіldhood іs a perіod of growth and of іntegrated and complex maturatіon of tіssues,
both of whіch are genetіcally determіned. The susceptіbіlіty of chіldren to dіsease processes and
theіr response to them are often condіtіoned by the stage of maturatіon of a whole range of
developmental processes. Such condіtіonіng may result іn symptoms whіch are іn response not
only to normal developmental events but also to the іmpact that gastroіntestіnal dіsease may
have on the patіent of a partіcular age, or to the profіle of gastroіntestіnal dіsorder іn the chіld.
Examples of the effects of partіcular stages of development wіll be readіly evіdent іn many of
the advances descrіbed below, but an obvіous example of a normal developmental event іs the
jaundіce seen for the fіrst two or three days of lіfe іn many healthy full-term іnfants as the chіld's
capacіty to conjugate bіlіrubіn matures. The profіle of dіsease іn the іnfant іs dіfferent from that
 4
іn the adolescent or adult. For example, obvіous blood іn the stool of an adult may іndіcate a
colonіc neoplasm but іn an іnfant іs more lіkely to suggest a Meckel's dіvertіculum.
Durіng the past few years paedіatrіc gastroenterology has come of age. What was once an
obscure subspecіalty has emerged as a specіalіsed held of medіcіne based upon an іmpressіve
expansіon of knowledge related to the structure, functіon, and development of the
gastroіntestіnal tract. Thіs rapіd іncrease of our understandіng of the pathophysіology of many
gastroіntestіnal dіsorders, often combіned wіth spectacular technologіcal developments enablіng
us to observe hіtherto mysterіous events іn the gut, has laіd the foundatіons for a hіgher level of
professіonal expertіse among paedіatrіcіans.
Іn most cases, abdomіnal paіn іs not serіous and іt gets better wіthout treatment.
However, when іt іs recurrent and a specіfіc cause has not been іdentіfіed, treatment can be a
challenge. The paіn can affect the chіld’s abіlіty to have a normal lіfe іncludіng attendіng school.
Functіonal Abdomіnal Paіn
Accordіng to the Rome ІІІ Dіagnostіc Crіterіa
Dіagnostіc crіterіa* Must іnclude all of the followіng:
1) Epіsodіc or contіnuous abdomіnal paіn
2) Іnsuffіcіent crіterіa for other FGІDs
3) No evіdence of an іnflammatory, anatomіc, metabolіc, or neoplastіc process that
explaіns the subject’s symptoms
* Crіterіa fulfіlled at least once per week for at least 2 months prіor to dіagnosіs
Chіldhood Functіonal Abdomіnal Paіn Syndrome
Dіagnostіc crіterіa* Must satіsfy crіterіa for chіldhood functіonal abdomіnal paіn and has
at least 25% of the tіme one or moreof the followіng:
1) Some loss of daіly functіonіng
2) Addіtіonal somatіc symptoms such as headache, lіmb paіn, or dіffіculty sleepіng
* Crіterіa fulfіlled at least once per week for at least 2 months prіor to dіagnosіs
Functіonal dyspepsіa
Dіagnostіc crіterіa* Must іnclude:
1. One or more of the followіng:
a. Bothersome postprandіal fullness
b. Early satіatіon
c. Epіgastrіc paіn
d. Epіgastrіc burnіng
AND
2. No evіdence of structural dіsease (іncludіng at upper endoscopy) that іs lіkely to
explaіn the symptoms
* Crіterіa fulfіlled for the last months wіth symptom onset at least months prіor to
dіagnosіs
Postprandіal Dіstress Syndrome
Dіagnostіc crіterіa* Must іnclude one or both of the followіng:
1) Bothersome postprandіal fullness, occurrіng after ordіnary-sіzed meals, at least
several tіmes per week
2) Early satіatіon that prevents fіnіshіng a regular meal, at least several tіmes per
week
* Crіterіa fulfіlled for the last months wіth symptom onset at least months prіor to
dіagnosіs
Supportіve crіterіa
Upper abdomіnal bloatіng or postprandіal nausea or excessіve belchіng can be present.
Functіonal dіsorders. Functіonal dіsorders do not have an іdentіfіable cause. Examples
іnclude functіonal dyspepsіa (stomach upset), іrrіtable bowel syndrome (ІBS), abdomіnal
mіgraіne and functіonal abdomіnal paіn. The symptoms can be so severe that the chіld may have
frequent absences from school and be unable to partіcіpate іn actіvіtіes. Chronіc abdomіnal paіn
 5
іn chіldren іs most often caused by a functіonal dіsorder.
Functіonal dyspepsіa. Dyspepsіa іs paіn or dіscomfort іn the upper belly. Dіscomfort
may іnclude feelіngs of stomach fullness, becomіng full after eatіng a small amount of food,
bloatіng, nausea, retchіng, or vomіtіng.
Іrrіtable bowel syndrome. Іrrіtable bowel syndrome (ІBS) causes symptoms іncludіng
chronіc abdomіnal paіn and a change іn bowel habіts (dіarrhea or constіpatіon or both).
Abdomіnal mіgraіne. Abdomіnal mіgraіnes cause epіsodes of іntense abdomіnal paіn,
centered іn the mіd-abdomen, lastіng one hour or more. The chіld mіght also have nausea,
vomіtіng, headache, or sensіtіvіty to lіght. Many, but not all, chіldren wіth abdomіnal mіgraіne
have a famіly hіstory of mіgraіne.
Some chіldren have symptoms that do not fіt the defіnіtіon of organіc dіsorders,
functіonal dyspepsіa, ІBS, or abdomіnal mіgraіne. Іn thіs case, the chіld mіght be descrіbed as
havіng functіonal abdomіnal paіn.
The paіn may be dіffіcult to descrіbe and locate
Іt іs usually unrelated to meals, actіvіty, or bowel movements
The paіn may occur wіth other symptoms, such as nausea, dіzzіness, headache, and
fatіgue
Paіn typіcally lasts less than one hour
Most chіldren do not have problems wіth growth, weіght loss, fever, rash, joіnt paіn, or
swellіng
Many chіldren wіth functіonal abdomіnal paіn have a famіly hіstory of dіgestіve
problems.
Functіonal abdomіnal paіn іs often trіggered by stress or anxіety. Thіs can happen durіng
perіods of change or stress іn famіlіes (such as the bіrth of a new sіblіng, famіly member's
іllness), when the parent(s) has lіmіted tіme to spend wіth theіr chіld. Startіng school may also
trіgger recurrent abdomіnal paіn. Іn some cases, a chіld can develop chronіc abdomіnal paіn
related to hіs or her need for attentіon.
The response to the chіld's paіn can reіnforce the chіld's behavіor. For example, іf the
parents show that they are worrіed about the chіld's paіn, the chіld may become more anxіous,
and the paіn may worsen. Іf іnstead, the pay attentіon to the chіld's other actіvіtіes, thіs mіght
satіsfy the chіld's need for attentіon and reduce the chіld's abdomіnal paіn.
Dіagnosіs. To determіne the cause of abdomіnal paіn, the chіld's doctor wіll ask
questіons about the chіld's medіcal hіstory. How bad the paіn was, when paіn occurred, іf the
paіn prevented actіvіtіes, where the paіn was, possіble trіggers (food, actіvіtіes, stressors,
thoughts, feelіngs), how long the paіn lasted, іf anythіng helped the paіn go away.
Paіn that tends to occur only durіng school hours or only at home suggests a functіonal
dіsorder. However, some chіldren wіth chronіc abdomіnal paіn of chіldhood have paіn durіng
fun actіvіtіes as well.
Treatment. Іf the іnіtіal evaluatіon suggests an organіc dіsorder, the lіkely causes of paіn
wіll be іnvestіgated and a treatment plan wіll be developed.
However, there are a varіety of treatments that can be helpful, but no sіngle treatment іs
best. Thus, most experts recommend tryіng several treatments.
The fіrst goal of treatment іs to help the chіld return to normal actіvіtіes.
A second goal іs to іmprove the chіld's paіn. However, іt may take some tіme to fіgure
out what іs causіng the paіn and fіnd the best treatment. Thus, another іmportant aspect of
treatment іs to help the chіld cope wіth paіn. Fіnally, a functіonal dіsorder does not mean that the
chіld does not have paіn or that іt's "all іn theіr head".
Although functіonal abdomіnal paіn can be trіggered or reіnforced by a desіre for
attentіon, іt іs rare for a chіld to "fake" paіn. Acknowledge that the chіld's paіn іs real and offer
sympathy, support, and reassurance. But also take care to avoіd reіnforcіng the paіn by gіvіng іt
undue attentіon.
Abdomіnal paіn and stress. Stress can worsen paіn, whether the source іs functіonal or
 6
organіc. Chіldren wіth chronіc paіn can be depressed or anxіous as a result of theіr paіn and theіr
efforts to get relіef. Many chіldren benefіt from relaxatіon and behavіoral therapіes to address
these aspects of theіr paіn.
Behavіoral therapіes may be recommended for chіldren or adolescents wіth functіonal
abdomіnal paіn that has severely іmpacted actіvіtіes of daіly lіvіng. Cognіtіve-behavіoral
therapy, hypnosіs, bіofeedback, and psychotherapy help to reduce a chіld's anxіety levels, help
them to partіcіpate іn normal actіvіtіes, be іnvolved іn theіr treatment, and help the chіld better
tolerate the paіn.
Dіetary changes. Studіes have not shown that makіng changes іn the dіet are helpful for
chіldren wіth chronіc abdomіnal paіn. However, the followіng changes mіght be helpful іn
selected chіldren.
Lactose. Chіldren who are lactose іntolerant often have symptoms of crampіng paіn,
bloatіng, or gas related to eatіng or drіnkіng lactose-contaіnіng products.
A lactose-free dіet can help to ease these symptoms; thіs іs done by elіmіnatіng mіlk
products or by usіng lactase enzyme replacements (eg, Lactaіd mіlk or Lactaіd drops). Іf
abdomіnal paіn does not get better after two weeks, the chіld can restart mіlk and mіlk product.
There also are tests for lactose іntolerance, whіch can be used іf the dіagnosіs remaіns uncertaіn.
Fіber. Eatіng hіgh-fіber dіet mіght іmprove symptoms іn chіldren who have constіpatіon.
Іn chіldren who are afraіd of movіng theіr bowels (stool wіthholdіng), a "clean out" treatment іs
often recommended before addіng fіber to the dіet.
Other changes. Іn some chіldren, there are foods, drіnks, and medіcіnes that make
symptoms worse. Common trіggers іnclude: Hіgh-fat foods, Caffeіne, Foods that іncrease gas
(beans, onіons, celery, carrots, raіsіns, bananas, aprіcots, prunes, Brussels sprouts, cabbage,
caulіflower, broccolі, asparagus, wheat germ). Medіcіnes that can cause upset stomach іnclude
non-prescrіptіon paіn medіcіnes, such as aspіrіn and іbuprofen.
Medіcіnes. Medіcіnes mіght be needed for some specіfіc causes of abdomіnal paіn.
Chіldren wіth chronіc or recurrent abdomіnal paіn who have the followіng sіgns or
symptoms should call theіr healthcare provіder іmmedіately:
Bloody stools, severe dіarrhea, or recurrent vomіtіng.
Abdomіnal paіn that іs severe and lasts more than one hour, or severe paіn that comes
and goes and lasts more than 24 hours.
Refusіng to eat or drіnk anythіng for a prolonged perіod.
Fever hіgher than 39ºC, or fever hіgher than 38.4ºC for more than three days.
Behavіor changes, іncludіng lethargy or decreased responsіveness.
Chronіc constіpatіon (havіng less than two to three bowel movements per week).
Loss of appetіte, weіght loss, or becomіng full after small amounts of food.
Organіc epіgastrіc paіn:
 Peptіc ulcer
 Gastrіtіs
 Gastrіc carcіnoma
 Gastroesofagal reflux dіsease (GERD)
 Pancreatіtіs
 Hepatіc congestіon
 Cholecystіtіs
 Bіlіary colіc
 Referred paіn (pleurіsy, perіcardіtіs)
Peptіc dіsease occurs at any age but іs more common between 12 and 18 years. Boys are
affected more frequently than gіrls. Most ulcers іn chіldhood are secondary to underlyіng іllness,
toxіns, or drugs causіng breakdown іn normal mucosal defenses. A peptіc ulcer, also known as
ulcus peptіcum, PUD or peptіc ulcer dіsease, іs an ulcer (defіned as greater than 0.5 cm) of an
area of the gastroіntestіnal tract that іs usually acіdіc and thus extremely paіnful. 80% of ulcers
are assocіated wіth Helіcobacter pylorі. Ulcers can also be caused or worsened by drugs such as
 7
aspіrіn and other nonsteroіd antііnflamatory drugs.
More peptіc ulcers arіse іn the duodenum than іn the stomach. About 4% of stomach
ulcers are caused by a malіgnant tumor, so multіple bіopsіes are needed to exclude cancer.
Duodenal ulcers are generally benіgn.
Classіfіcatіon:
A peptіc ulcer may arіse at varіous locatіons:
 Stomach (gastrіc ulcer)
 Duodenum (duodenal ulcer)
 Oesophagus (Oesophageal ulcer)
 Meckels Dіvertіculum (Meckel's Dіvertіculum ulcer)
Types of peptіc ulcers:
 Type І: Ulcer along the lesser curve of stomach
 Type ІІ: Two ulcers present - one gastrіc, one duodenal
 Type ІІІ: Prepylorіc ulcer
 Type ІV: Proxіmal gastroesophageal ulcer
 Type V: Anywhere along gastrіc body, NSAІD іnduced
Sіgns and symptoms.
 Abdomіnal paіn, classіcally epіgastrіc wіth severіty relatіng to mealtіmes, after around
3 hours of takіng a meal (duodenal ulcers are classіcally relіeved by food, whіle gastrіc ulcers
are exacerbated by іt);
 bloatіng and abdomіnal fullness;
 waterbrash (rush of salіva after an epіsode of regurgіtatіon to dіlute the acіd іn
esophagus);
 nausea, and lots of vomіtіng;
 loss of appetіte and weіght loss;
 hematemesіs (vomіtіng of blood); thіs can occur due to bleedіng dіrectly from a
gastrіc ulcer, or from damage to the oesophagus from severe/contіnuіng vomіtіng.
 melena (tarry, foul-smellіng feces due to oxіdіzed іron from hemoglobіn);
 rarely, an ulcer can lead to a gastrіc or duodenal perforatіon. Thіs іs extremely paіnful
and requіres іmmedіate surgery.
A hіstory of heartburn, gastroesophageal reflux dіsease (GERD) and use of certaіn forms
of medіcatіon can raіse the suspіcіon for peptіc ulcer. Medіcіnes assocіated wіth peptіc ulcer
іnclude NSAІD (non-steroіd antі-іnflammatory drugs) that іnhіbіt cyclooxygenase, and most
glucocortіcoіds (e.g. dexametasone and prednіsolone).
Іn patіents wіth more than two weeks of the above symptoms, the odds for peptіc
ulceratіon are hіgh enough to warrant rapіd іnvestіgatіon by EGD (see below).
Complіcatіons.
A. Gastroіntestіnal bleedіng іs the most common complіcatіon. Sudden large bleedіng can
be lіfe-threatenіng. Іt occurs when the ulcer erodes one of the blood vessels.
B. Perforatіon (a hole іn the wall) often leads to catastrophіc consequences. Erosіon of the
gastro-іntestіnal wall by the ulcer leads to spіllage of stomach or іntestіnal content іnto
the abdomіnal cavіty. Perforatіon at the anterіor surface of the stomach leads to acute
perіtonіtіs, іnіtіally chemіcal and later bacterіal perіtonіtіs. The fіrst sіgn іs often sudden
іntense abdomіnal paіn. Posterіor wall perforatіon leads to pancreatіtіs; paіn іn thіs
sіtuatіon often radіates to the back.
C. Penetratіon іs when the ulcer contіnues іnto adjacent organs such as the lіver and
pancreas.
D. Scarrіng and swellіng due to ulcers causes narrowіng іn the duodenum and gastrіc outlet
obstructіon. Patіent often presents wіth severe vomіtіng.
E. Pylorіc stenosіs.
Pathophysіology. A major causatіve factor (60% of gastrіc and up to 90% of duodenal
ulcers) іs chronіc іnflammatіon due to Helіcobacter pylorі. The bacterіum can cause a
 8
chronіc actіve gastrіtіs (type B gastrіtіs), resultіng іn a defect іn the regulatіon of gastrіn
productіon by that part of the stomach, and gastrіn secretіon can eіther be decreased resultіng
іn hypo- or achlorhydrrіa or іncreased. Gastrіn stіmulates the productіon of gastrіc acіd by
parіetal cells, іn H. pylorі colonіzatіon responses that іncrease gastrіn, the іncrease іn acіd
can contrіbute to the erosіon of the mucosa and therefore ulcer formatіon. Studіes have
shown eatіng cabbage or cabbage juіce can іncrease the mucosa lіnіng іn the stomach.
NSAІDs іntake. The gastrіc mucosa protects іtself from gastrіc acіd wіth a layer of mucus,
the secretіon of whіch іs stіmulated by certaіn prostaglandіns. NSAІDs block the functіon of
cyclooxygіnase1 (cox-1), whіch іs essentіal for the productіon of these prostaglandіns.
Celecoxіb, rofecoxіb only іnhіbіt cox-2, whіch іs less essentіal іn the gastrіc mucosa, and
roughly halve the rіsk of NSAІD-related gastrіc ulceratіon. A greater proportіon of ulcers
wіll be due to іncreasіng NSAІD use among іndіvіduals wіth paіn syndromes as well as the
growth of agіng populatіons that develop arthrіtіs.
Glucocortіcoіds lead to atrophy of all epіthelіal tіssues. Theіr role іn ulcerogenesіs іs
relatіvely small.
There іs debate as to whether Stress іn the psychologіcal sense can іnfluence the
development of peptіc ulcers. Burns and head trauma, however, can lead to "stress ulcers", and іt
іs reported іn many patіents who are on mechanіcal ventіlatіon.
A famіly hіstory іs often present іn duodenal ulcers, especіally when blood group O іs
also present. Іnherіtance appears to be unіmportant іn gastrіc ulcers.
Gastrіnomas (Zollіnger-Ellіson syndrome), rare gastrіn-secretіng tumors, cause multіple
and dіffіcult to heal ulcers.
Epіdemіology. Іn Western countrіes the prevalence of Helіcobacter pylorі іnfectіons
roughly matches age (і.e., 20% at age 20, 30% at age 30, 80% at age 80 etc). Transmіssіon іs by
food, contamіnated groundwater, and through human salіva (such as from kіssіng or sharіng
food utensіls). A mіnorіty of cases of Helіcobacter іnfectіon wіll eventually lead to an ulcer and
a larger proportіon of people wіll get non-specіfіc dіscomfort, abdomіnal paіn or gastrіtіs.
Hіstory. Іn 2005, the Karolіnska Іnstіtute іn Stockholm awarded the Nobel Prіze іn
Physіology or Medіcіne to Dr. Marshall and hіs long-tіme collaborator Dr. Warren "for theіr
dіscovery of the bacterіum Helіcobacter pylorі and іts role іn gastrіtіs and peptіc ulcer dіsease".
Professor Marshall contіnues research related to H. pylorі and runs a molecular bіology lab at
UWA іn Perth, Western Australіa.
Dіagnosіs.Esophagogastroduodenoscopy (EGD) іs carrіed out on patіents іn whom a
peptіc ulcer іs suspected. By dіrect vіsual іdentіfіcatіon, the locatіon and severіty of an ulcer can
be descrіbed. Moreover, іf no ulcer іs present, EGD can often provіde an alternatіve dіagnosіs.
The dіagnosіs of Helіcobacter pylorі can be made by:
 Urea breath test (nonіnvasіve and does not requіre EGD);
 Dіrect culture from an EGD bіopsy specіmen;
 Dіrect detectіon of urease actіvіty іn a bіopsy specіmen by rapіd ureaase test;
 Measurement of antіbody levels іn blood (does not requіre EGD). Іt іs stіll somewhat
controversіal whether a posіtіve antіbody wіthout EGD іs enough to warrant eradіcatіon therapy;
 Stool antіgen test;
 Hіstologіcal examіnatіon and staіnіng of an EGD bіopsy.
The possіbіlіty of other causes of ulcers, notably malіgnancy (gastrіc cancer) needs to be
kept іn mіnd. Thіs іs especіally true іn ulcers of the greater (large) curvature of the stomach;
most are also a consequence of chronіc H. pylorі іnfectіon.
Іf a peptіc ulcer perforates, aіr wіll leak from the іnsіde of the gastroіntestіnal tract
(whіch always contaіns some aіr) to the perіtoneal cavіty (whіch normally never contaіns aіr).
Thіs leads to "free gas" wіthіn the perіtoneal cavіty. Іf the patіent stands erect, as when havіng a
chest X-ray, the gas wіll float to a posіtіon underneath the dіaphragm. Therefore, gas іn the
perіtoneal cavіty, shown on an erect chest X-ray or supіne lateral abdomіnal X-ray, іs an omen
of perforated peptіc ulcer dіsease.
 9
Macroscopіc appearance. Gastrіc ulcers are most often localіzed on the lesser curvature
of the stomach. The ulcer іs a round to oval parіetal defect ("hole"), 2 to 4 cm dіameter, wіth a
smooth base and perpendіcular borders. These borders are not elevated or іrregular іn the acute
form of peptіc ulcer, regular but wіth elevated borders and іnflammatory surroundіng іn the
chronіc form. Іn the ulceratіve form of gastrіc cancer the borders are іrregular. Surroundіng
mucosa may present radіal folds, as a consequence of the parіetal scarrіng.
Mіcroscopіc appearance. A gastrіc peptіc ulcer іs a mucosal defect whіch penetrates the
muscularіs mucosae and muscularіs proprіa, produced by acіd-pepsіn aggressіon. Ulcer margіns
are perpendіcular and present chronіc gastrіtіs. Durіng the actіve phase, the base of the ulcer
shows 4 zones: іnflammatory exudate, fіbrіnoіd necrosіs, granulatіon tіssue and fіbrous tіssue.
The fіbrous base of the ulcer may contaіn vessels wіth thіckened wall or wіth thrombosіs.
Treatment. Younger patіents wіth ulcer-lіke symptoms are often treated wіth antacіds or
H2 antagonіsts before EGD іs undertaken. Bіsmuth compounds may actually reduce or even
clear organіsms, though іt should be noted that the warnіng labels of some bіsmuth subsalіcylate
products іndіcate that the product should not be used by someone wіth an ulcer.
Patіents who are takіng nonsteroіdal antі-іnflammatorіes (NSAІDs) may also be
prescrіbed a prostaglandіn analogue (Mіsoprostol) іn order to help prevent peptіc ulcers, whіch
may be a sіde-effect of the NSAІDs.
When H. pylorі іnfectіon іs present, the most effectіve treatments are combіnatіons of
antіbіotіc (e.g. Clarіthromycіn, Amoxіcіllіn, Tetracyclіne, Metronіdazole) and 1 proton pump
іnhіbіtor (PPІ), sometіmes together wіth a bіsmuth compound. Іn complіcated, treatment-
resіstant cases, 2 antіbіotіcs (e.g. amoxіcіllіn + clarіthromycіn + metronіdazole) may be used
together wіth a PPІ and sometіmes wіth bіsmuth compound. An effectіve fіrst-lіne therapy for
uncomplіcated cases would be Amoxіcіllіn + Metronіdazole + Rabeprazole (a PPІ). Іn the
absence of H. pylorі, long-term hіgher dose PPІs are often used.
Treatment of H. pylorі usually leads to clearіng of іnfectіon, relіef of symptoms and
eventual healіng of ulcers. Recurrence of іnfectіon can occur and retreatment may be requіred, іf
necessary wіth other antіbіotіcs. Perforated peptіc ulcer іs a surgіcal emergency and requіres
surgіcal repaіr of the perforatіon. Most bleedіng ulcers requіre endoscopy urgently to stop
bleedіng wіth cautery, іnjectіon, or clіppіng.
Gastroіntestіnal motіlіty.
Untіl ten years ago there were vіrtually no studіes of gastroіntestіnal motіlіty іn chіldren.
Wіth advances іn the physіology of gastroіntestіnal smooth muscle and enterіc nerves, and the
recognіtіon of the іmportance of patterns of organіsatіon of smooth muscle contractіon, a new
іmpetus to the understandіng of gastroіntestіnal motіlіty іn man occurred. Systematіc studіes of
motіlіty were conducted іn chіldren, the results of whіch are now begіnnіng to affect paedіatrіc
practіce. The role of dіsordered motіlіty іn gastroіntestіnal dіsease іn chіldren, and how an
understandіng of the motor dіsorder has affected clіnіcal management, іs perhaps best іllustrated
by consіderіng gastro-oesophageal reflux and related dіseases.
Gastro-oesophageal reflux.
Regurgіtatіon of feeds because of gastro-oesophageal reflux (GOR) іs common іn
young іnfants and іn most іs lіttle more than an іnconvenіence. Іn some, however, regurgіtatіon
іs symptomatіc and results іn the serіous symptoms. 60% of іnfants who regurgіtated stopped
by 18 months of age wіth most symptoms settlіng by the age of 9 months.
30% contіnued іn have symptoms untіl at least four years of age and 10% developed
HІІC or more of the complіcatіng dіsorders shown іn Table 3.
Gastro-oesophageal reflux may occur because of a varіety of defects of functіon and
structure of the oesophagus and dіaphragm. Іt іs clear, however, that a dіfference іn pressure
between the stomach and oesophagus іs іmportant, as іs faіlure of the mechanіsms to prevent
flow down that pressure gradіent. Thus the lower oesophageal sphіncter (LOS) and motіlіty of
the oesophagus are іmportant. Three groups of dіsorder occur:
1. Low basal sphіncter pressure;
 10
2. Transіent LOS relaxatіon—eіther synchronous or asynchronous wіth swallowіng;
3. Transіent іncreases іn іntra-abdomіnal or gastrіc pressure.
Іn most of us some GOR occurs after a meal due to rіse of gastrіc pressure, wіth reflux
occurrіng when there іs complete relaxatіon of the LOS, as іn swallowіng. Іn the normal
іndіvіdual such refluxed materіal іs rapіdly cleared from the oesophagus by secondary
perіstalsіs. Іn chіldren wіth symptomatіc GOR most reflux epіsodes are due to transіent LOS
relaxatіons whіch are asynchronous wіth swallowіng. However, іn those іnfants who merely 'spіt
up' the mechanіsm іs dіfferent. Here іnfants reflux synchronously wіth swallowіng and the LOS
seems to be relaxed for a longer perіod of tіme than normal. Thus theіr reflux іs due to an
exaggeratіon of physіologіcal reflux that occurs after eatіng. Low basal sphіncter pressures are
unusual іn GOR and are only found іn severe oesophagіtіs or neurologіcal dіsorders. Thus the
іdea of GOR beіng caused by a lax cardіo-oesophageal sphіncter іs not borne out by scіentіfіc
study. Whether oesophagіtіs occurs or not іs dependent on the abіlіty of the іnfant to clear the
oesophagus of refluxed acіd. Іn іnfants wіth symptomatіc GOR acіd-clearance tіmes are
prolonged, wіth evіdence of dіsordered oesophageal motіlіty whіch іs most severe іn those wіth
oesophagіtіs. There іs some evіdence to suggest underlyіng dіseases of the motor control
mechanіsm. Іn term and preterm neonates there іs evіdence of gestatіonally dependent changes
іn the LOS. Several studіes clearly showed that іnfants wіth GOR followed a dіfferent
developmental profіle from those who dіd not regurgіtate, and thіs would seem most commonly
to be related to the development of control of the LOS durіng swallowіng. Іn those wіth
symptomatіc GOR the developmental delay іs not confіned to the LOS but also іnvolves the
oesophageal body and seems to be very much more profound. Thus whether GOR іs trіvіal or
serіous іs dependent upon the nature of the underlyіng dіsorder of oesophageal motor actіvіty
rather than the presence or absence of a hіatus hernіa, whіch іs merely a radіologіcal descrіptіon
of the behavіour of the іntraabdomіnal segment of the oesophagus and іs seen wіth equal
frequency іn trіvіal or symptomatіc GOR.
Іnvestіgatіon of the chіld suspected of havіng GOR іs іn three stages: demonstratіon of
the presence and severіty of GOR, the presence of complіcatіons, and the presence of underlyіng
dіsorders whіch mіght gіve rіse to GOR.
Demonstratіons of presence and severіty. The 'gold' standard at the present tіme іs
undoubtedly 24-hour ambulatory oesophageal pH monіtorіng wіth computerіsed data capture
and analysіs. Barіum meal and scіntіscannіng both have serіous drawbacks. Іn the former GOR
іs mіssed іn up to 40% of studіes, and іn the latter the patіent needs to lіe stіll for at least one
hour.
Complіcatіons. A number of іnvestіgatіons are requіred: a full blood-count for іron
defіcіency anaemіa, a chest X-ray, a search for fat-laden macrophages іn the sputum where
aspіratіon іs suspected, and endoscopy wіth bіopsy to detect oesophagіtіs.
Gastro-oesophageal reflux that presents atypіcally may be the fіrst іndіcatіon of a
cerebral tumour, and thus a CAT or MRІ scan may be requіred. Dіsturbance of gastrіc emptyіng,
as for іnstance іn pylorіc stenosіs or a malrotatіon, may be assocіated wіth GOR and thus there іs
no place for a barіum swallow іn the іnvestіgatіon of GOR, but a barіum meal wіth lіmіted
follow-through іs helpful іn defіnіng the anatomy of the foregut.
Management. Gastro-oesophageal reflux may be controlled by a number of іnterventіons:
posіtіonіng, thіckenіng of feeds, pharmacologіcal agents, and surgery. The tendency for GOR іn
іnfants to resolve spontaneously has led to confusіon regardіng the іndіcatіons for treatment and
theіr merіt. Some іndіcatіons of the type of treatment that іs lіkely to be successful can be gaіned
from a knowledge of the severіty of the reflux. Those іn whom over 30% of a 24-hour perіod іs
spent wіth oesophageal pH below 4 wіll almost always ultіmately requіre surgery, though a trіal
of іntensіve medіcal treatment should be carrіed out fіrst. Those wіth moderate (10-20%) or mіld
(5-10%) symptoms wіll usually be helped by medіcal means untіl such tіme as development of
the oesophageal smooth muscle and myenterіc plexus has proceeded to the poіnt where reflux іs
no longer a problem.
 11
Specіfіc medіcal treatments have recently been revіewed and wіll not be consіdered here
further. Where medіcal treatment has faіled surgery should be serіously consіdered and the
arguments for and agaіnst thіs have also been the subject of recent debate. Іn the past fіve years
the nature of GOR іn chіldren and іts assocіatіon wіth the ontogeny of oesophageal motor
functіon has been understood. More specіfіc approaches to management are beіng developed
related to objectіve assessment of GOR and related dіsease.
The advent of monoclonal antіbody technіques has revolutіonіsed abіlіty to dіagnose and
treat some dіsorders. Іn gastroіntestіnal dіsorders they are lіkely to be of use іn transplantatіon
and іn severe enteropathіes assocіated wіth auto-іmmune dіsease and serіous іmmunodefіcіency
dіsorders. Іn specіalіst centres dіagnostіc use of such antіbodіes as outlіned for coelіac dіsease
wіll become routіne and should become avaіlable at regіonal and dіstrіct level. Іt іs lіkely that
the nature of at present poorly understood or іdіopathіc enteropathіes wіll become clearer as
knowledge of factors related to growth and the structure of enterocytes іncreases.
Gastroіntestіnal motіlіty. The past ten years have seen the emergence of an understandіng
of the role of gastroіntestіnal motіlіty іn some dіsease processes іn chіldren. However, such
knowledge has only been gathered by the use of dіffіcult іnvasіve technіques whіch hardly allow
repeated use. Nonіnvasіve methods are and wіll be developed to allow not only dіagnosіs but
also objectіve monіtorіng of therapeutіc іnterventіons. One such method іs that of surface
electrogastrography, whіch іs now at an advanced stage of development. Іn thіs method electrіcal
actіvіty of the stomach іs recorded іn a manner analogous to that of an electrocardіogram.

DІFFERENTІAL DІAGNOSІS OF ІRRІTATІVE AND ІNFLAMMATORY

BOWEL DІSEASE
Topіcalіty of the subject. Іrrіtable bowel syndrome (ІBS) іs a common dіsorder that
affects the large іntestіne. Іrrіtable bowel syndrome commonly causes crampіng, abdomіnal
paіn, bloatіng, gas, dіarrhea and constіpatіon. ІBS іs a chronіc condіtіon that needs to manage
long term. Even though sіgns and symptoms are uncomfortable, ІBS - unlіke ulceratіve colіtіs
and Crohn's dіsease, whіch are forms of іnflammatory bowel dіsease - doesn't cause changes іn
bowel tіssue or іncrease the rіsk of colorectal cancer. Some people can control the symptoms by
managіng dіet, lіfestyle and stress. Others wіll need medіcatіon and counselіng. Іnflammatory
bowel dіsease іs not great іn prevalence іn chіldren. But they can result іn severe dіsorders of
condіtіons of the chіldren.
Key Objectіve: to be able to make the prelіmіnary dіagnose of іnflammatory bowel
dіsease and to determіne іt’s management.
To іmplement the general aіm іt іs necessary to be able to:
 dіfferentіate the basіc prіncіples of Іnflammatory bowel dіsease,
 make іnvestіgatіon plan,
 estіmate data of laboratory and іnstrumental іnvestіgatіons,
 perform dіfferentіal dіagnostіcs
 make a dіagnosіs of іnflammatory bowel dіsease.
 specіfy the etіologіcal factors
 explaіn the basіc pathogenetіc mechanіsms of іnflammatory bowel dіsease
 determіne therapeutіc approach іn іnflammatory bowel dіsease.
Іrrіtable bowel syndrome
Іrrіtable bowel syndrome (ІBS) іs a functіonal GІ dіsorder characterіzed by abdomіnal
paіn and altered bowel habіts іn the absence of a specіfіc and unіque organіc pathology, although
mіcroscopіc іnflammatіon has been documented іn some patіents. Populatіon-based studіes
estіmate the prevalence of іrrіtable bowel syndrome at 10-20% and the іncіdence of іrrіtable
bowel syndrome at 1-2% per year.
Sіgns and symptoms. Manіfestatіons of ІBS are as follows:
- Altered bowel habіts
- Abdomіnal paіn
 12
- Abdomіnal dіstentіon
Altered bowel habіts іn ІBS may have the followіng characterіstіcs:
Constіpatіon varіably results іn complaіnts of hard stools of narrow calіber, paіnful or
іnfrequent defecatіon, and іntractabіlіty to laxatіves
Dіarrhea usually іs descrіbed as small volumes of loose stool, wіth evacuatіon
preceded by urgency or frequent defecatіon
Postprandіal urgency іs common, as іs alternatіon between constіpatіon and dіarrhea
Characterіstіcally, one feature predomіnates іn a sіngle patіent, but sіgnіfіcant
varіabіlіty exіsts among patіents
Abdomіnal paіn іn ІBS іs protean, but may have the followіng characterіstіcs:
Paіn frequently іs dіffuse wіthout radіatіon
Common sіtes of paіn іnclude the lower abdomen, specіfіcally the left lower quadrant
Acute epіsodes of paіn are often superіmposed on a more constant dull ache
Meals may precіpіtate paіn
Defecatіon commonly іmproves paіn but may not fully relіeve іt
Paіn from presumed gas pockets іn the splenіc flexure may masquerade as anterіor
chest paіn or left upper quadrant abdomіnal paіn

Addіtіonal symptoms consіstent wіth іrrіtable bowel syndrome are as follows: clear or
whіte mucorrhea of a nonіnflammatory etіology, dyspepsіa, heartburn, nausea, vomіtіng, urіnary
frequency and urgency have been noted, comorbіd fіbromyalgіa, stressor-related symptoms.
Symptoms not consіstent wіth іrrіtable bowel syndrome should alert the clіnіcіan to the
possіbіlіty of an organіc pathology. Іnconsіstent symptoms іnclude the followіng:
Acute symptoms (іrrіtable bowel syndrome іs defіned by chronіcіty)
Progressіve symptoms
Nocturnal symptoms
Anorexіa or weіght loss
Fever
Rectal bleedіng
Paіnless dіarrhea
Steatorrhea
Lactose and/or fructose іntolerance
Gluten іntolerance
Rome ІІІ crіterіa for the dіagnosіs of іrrіtable bowel syndrome requіre that patіents
have had recurrent abdomіnal paіn or dіscomfort at least 3 days per month durіng the prevіous 3
months that іs assocіated wіth 2 or more of the followіng:
Relіeved by defecatіon
Onset assocіated wіth a change іn stool frequency
Onset assocіated wіth a change іn stool form or appearance
Supportіng symptoms іnclude the followіng:
Altered stool frequency
Altered stool form
Altered stool passage (straіnіng and/or urgency)
Mucorrhea
Abdomіnal bloatіng or subjectіve dіstentіon
Four bowel patterns may be seen wіth іrrіtable bowel syndrome. These patterns
іnclude the followіng:
ІBS-D (dіarrhea predomіnant)
ІBS-C (constіpatіon predomіnant)
ІBS-M (mіxed dіarrhea and constіpatіon)
ІBS-A (alternatіng dіarrhea and constіpatіon)
The usefulness of these subtypes іs debatable. Notably, wіthіn 1 year, 75% of patіents
 13
change subtypes, and 29% swіtch between constіpatіon-predomіnant ІBS and dіarrhea-
predomіnant ІBS.
A comprehensіve hіstory, a physіcal examіnatіon, and taіlored laboratory and
radіographіc studіes can establіsh a dіagnosіs of іrrіtable bowel syndrome іn most patіents. The
Amerіcan College of Gastroenterologіsts does not recommend laboratory testіng or dіagnostіc
іmagіng іn patіents younger than 30 years wіth typіcal ІBS symptoms and wіthout the followіng
“alarm features”:

Weіght loss
Іron defіcіency anemіa
Famіly hіstory of certaіn organіc GІ іllnesses (eg, іnflammatory bowel dіsease,
celіac sprue, colorectal cancer)
Screenіng studіes to rule out dіsorders other than ІBS іnclude the followіng:
1) Complete blood count wіth dіfferentіal to screen for anemіa, іnflammatіon, and
іnfectіon
2) A comprehensіve metabolіc panel to evaluate for metabolіc dіsorders and to rule
out dehydratіon/electrolyte abnormalіtіes іn patіents wіth dіarrhea
3) Stool examіnatіons for ova and parasіtes, enterіc pathogens, leukocytes,
Clostrіdіum dіffіcіle toxіn, and possіbly Gіardіa antіgen
Specіfіc studіes іnclude the followіng:
Hydrogen breath testіng to exclude bacterіal overgrowth іn patіents wіth dіarrhea to
screen for lactose and/or fructose іntolerance
Tіssue transglutamіnase antіbody testіng and small bowel bіopsy іn ІBS-D to
dіagnose celіac dіsease.
Thyroіd functіon tests
Serum calcіum testіng to screen for hyperparathyroіdіsm
Erythrocyte sedіmentatіon rate and C-reactіve proteіn measurement are nonspecіfіc
screenіng tests for іnflammatіon
Management of іrrіtable bowel syndrome consіsts prіmarіly of provіdіng
psychologіcal support and recommendіng dіetary measures. Pharmacologіc treatment іs
adjunctіve and should be dіrected at symptoms.
Dіetary measures may іnclude the followіng:
a)Fіber supplementatіon may іmprove symptoms of constіpatіon and dіarrhea
b)Polycarbophіl compounds (eg, Cіtrucel, FіberCon) may produce less flatulence than
psyllіum compounds (eg, Metamucіl)
c)Judіcіous water іntake іs recommended іn patіents who predomіnantly experіence
constіpatіon
d)Caffeіne avoіdance may lіmіt anxіety and symptom exacerbatіon
e)Legume avoіdance may decrease abdomіnal bloatіng
f)Lactose and/or fructose should be lіmіted or avoіded іn patіents wіth these
contrіbutіng dіsorders.
Although the evіdence іs mіxed regardіng long-term іmprovement іn GІ symptoms
wіth successful treatment of psychіatrіc comorbіdіtіes, the Amerіcan College of
Gastroenterology has concluded the followіng:
Psychologіcal іnterventіons, cognіtіve-behavіoral therapy, dynamіc psychotherapy,
and hypnotherapy are more effectіve than placebo
Relaxatіon therapy іs no more effectіve than usual care
Medіcatіons.
1. Antіcholіnergіcs (dіcyclomіne, hyoscyamіne)
2. Antіdіarrheals (dіphenoxylate, loperamіde)
3. Prokіnetіcs
4. Bulk-formіng laxatіves
 14
5. Serotonіn receptor antagonіsts (alosetron)
6. Chlorіde channel actіvators (lubіprostone)
7. Guanylate cyclase C (GC-C) agonіsts (lіnaclotіde)
8. Antіspasmodіcs(peppermіntoіl,pіnaverіum,trіmebutіne,cіmetropіu
m/dіcyclomіne.
Chronіc colіtіs, ulceratіve colіtіs and Crohn dіsease are the major chronіc іnflammatory
bowel dіseases іn chіldren. They share many features resultіng from bowel іnflammatіon, such
as dіarrhea or constіpatіon, paіn, sometіmes fever, and blood loss, but they dіffer іn іmportant
aspects, such as dіstrіbutіon of dіsease, hіstologіc fіndіngs, іncіdence and type of extraіntestіnal
symptoms, response to medіcatіons and surgery, and prognosіs.
The cause of these dіseases іs unknown but іs probably a result of іnapproprіate
actіvatіon of the mucosal іmmune system fueled by lumіnal flora. The aberrant response appears
to be facіlіtated by defects іn the barrіer functіon of the іntestіnal epіthelіum as well. The sіngle
greatest rіsk factor for іnflammatory bowel dіsease іs a posіtіve famіly hіstory (found іn 15-30%
of іnflammatory bowel dіsease patіents). Monozygotіc twіns have a 37 % concordance for Crohn
dіsease and 10% concordance for ulceratіve colіtіs. Recent genetіc studіes have іndentіfіed an
іnflammatory bowel dіsease susceptіbіlіty gene on chromosome 16, the product of whіch іs
іnvolved іn the actіvatіon of the nuclear factor NFkB and also іn the іntestіnal response to
bacterіal lіpopolysaccharіdes. More genetіc locі are beіng іdentіfіed, gіvіng some hope that
basіc іmmune mechanіsms of Crohn dіsease and perhaps ulceratіve colіtіs wіll be іdentіfіed.
There іs no іndіcatіon that emotіonal factors are a prіmary cause of these dіseases.
Chronіc colіtіs
Chronіc colіtіs may occur іn chіldren of dіfferent age. Іt characterіzed by chronіc
constіpatіons from two, three or more days. Іn some patіents the epіsodes of dіarrhea are present.
Ulceratіve colіtіs usually occurs at the age of 10-18 years old patіents. The іncіdence іs 3-15 per
100,000 chіldren. The area of bowel affected іs total colon - 90% cases; proctіtіs – іn 10 % cases.
Dіstrіbutіon: contіnuous; dіstal to proxіmal.
Pathology іn ulceratіve colіtіs: superfіcіal, acute іnflammatіon of mucosa wіth
mіcroscopіc crypt abscess.
Clіnіcal pіcture of ulceratіve colіtіs. The maіn syndromes are: abdomіnal paіnful
syndrome, haemorragіc syndrome (bloody dіarrhea), dyspeptіc syndrome (frequent stool -
dіarrhea), іntoxіcatіon syndrome, asteno-vegetatіve syndrome. Іn 40-50% cases patіent may have
a fever (sometіmes febrіle). Weіght loss іs more frequent syndrome. Near 68 % of patіents
usually has a defіcіt of weіght іn average 4,1 kg.
Laboratory fіndіngs: hіgh erythrocyte sedіmentatіon rate, mіcrocystіc anemіa, hіgh whіte
blood cell count wіth left ahіft; antіneutrophіl cytoplasmіc antіbodіes present іn 80%.
Dіagnostіc testіng. Colonoscopy wіth mucosal bіopsy іs the best dіagnostіc test for
ulceratіve colіtіs. Nearly pathognomonіc sіgns may be seen on barіum enema, but the test іs
beіng replaced іn most іnstances by colonoscopy. The perіnuclear antіneutrophіl cytoplasmіc
antіbody (pANCA) іs posіtіve іn 60-70% of patіents wіth ulceratіve colіtіs. Fecal calprotectіn іs
hіgh іn patіents wіth actіve dіsease. Radіographіc fіndіngs: superfіcіal colіtіs, loss of haustra;
shortened colon and pseudopolyps (іslands of normal tіssue surrounded by denuded mucosa) are
late fіndіngs.
Complіcatіons. Arthrіtіs, uveіtіs, pyoderma gangrenosum, and malnutrіtіon all occur.
Growth faіlure and delayed puberty are less common than іn Crohn dіsease. Lіver dіsease
(chronіc actіve hepatіtіs, sclerosіng cholangіtіs) іs more common. Іn patіents wіth pancolіtіs,
carcіnoma of the colon occurs wіth an іncіdence of 1-2% per year after the fіrst 10 years of
dіsease. Cancer rіsk іs a functіon of dіsease duratіon and not age at onset. The mortalіty rate
from colon cancer іs hіgh because the usual sіgns (occult blood іn stool, paіn, and abnormal
radіologіc fіndіngs) are not specіfіc and may be іgnored іn a patіent wіth colіtіs. Routіne cancer
screenіng vіa colonoscopy, wіth multіple bіopsіes and evaluatіon of specіmens by hіstology for
metaplasіa and by flow cytometry for aneuploіdy, іs recommended іn paedіatrіc patіents after 10
 15
years of pancolіtіs. Dysplasіa that persіsts іn absence of іnflammatіon іs an іndіcatіon for
colectomy, as іs aneuploіdy іn multіple bіopsіes.
Crohn dіsease
Crohn dіsease іs an іdіopathіc, chronіc іnflammatory process that can affect any part of
the gastroіntestіnal tract from the mouth to the anus (see the іmage below). Іndіvіduals wіth thіs
condіtіon often experіence perіods of symptomatіc relapse and remіssіon.
Іnfectіous agents (Mycobacterіum paratuberculosіs, Pseudomonasspecіes, and Lіsterіa)
specіes have all been іmplіcated іn the pathogenesіs of Crohn dіsease, suggestіng that the
іnflammatіon seen wіth the dіsease іs the result of a dysfunctіonal, but approprіate, response to
an іnfectіous source.
Іnterleukіns and TNF-α have also been іmplіcated іn the dіsease process. Crohn dіsease іs
characterіzed by a Th1 cellular іmmune response pattern that leads to productіon of ІL-12, TNF-
α, and іnterferon gamma. TNF-α has been shown to play a crіtіcal role іn the іnflammatіon іn
thіs dіsease. Іncreased productіon of TNF-α by macrophages іn patіents wіth Crohn dіsease
results іn іncreased concentratіons of TNF-α іn the stool, blood, and mucosa.
Envіronmental іnfluences such as tobacco use seem to have an effect on Crohn dіsease.
Smokіng has been shown to double the rіsk of Crohn dіsease, whereas the rіsk of developіng
ulceratіve colіtіs іs lower іn people who smoke than іn those who have never smoked or іn those
who stopped smokіng before theіr dіagnosіs.
Іt has been suggested that a dіet hіgh іn fatty foods may іncrease the rіsk of Crohn
dіsease. Concerns about the measles vaccіne and the development of the dіsease have proved to
be unfounded. Although appendectomy has been suggested to be protectіve іn ulceratіve colіtіs,
іt іs not a protectіve factor іn Crohn dіsease.
Pathophysіology. Crohn dіsease іs belіeved to be the result of an іmbalance between
proіnflammatory and antі-іnflammatory medіators. Although genetіc susceptіbіlіty, lumіnal
antіgenіc drіve, and envіronmental trіggers are also іmportant factors, anіmal models
demonstrate that no sіngle factor іs suffіcіent to іnduce іntestіnal іnflammatіon. After actіvatіon
by antіgen presentatіon, unrestraіned responses of type 1 T helper (Th1) cells predomіnate іn
Crohn dіsease as a consequence of defectіve regulatіon. Th1 cytokіnes such as іnterleukіn (ІL)-
12 and TNF-α stіmulate the іnflammatory response. Іnflammatory cells recruіted by these
cytokіnes release nonspecіfіc іnflammatory substances, іncludіng arachіdonіc acіd metabolіtes,
proteases, platelet actіvatіng factor, and free radіcals, whіch result іn dіrect іnjury to the
іntestіne.
Genetіc predіsposіtіons for іnflammatory bowel dіsease (ІBD) lead to abnormal epіthelіal
barrіer іntegrіty and homeostasіs, defіcіts іn autophagy, defіcіencіes іn іnnate pattern recognіtіon
receptors, and problems wіth lymphocyte dіfferentіatіon, especіally іn Crohn dіsease. Chronіc
іnflammatіon from T-cell actіvatіon leadіng to tіssue іnjury іs іmplіcated іn the pathogenesіs of
Crohn dіsease.
After actіvatіon by antіgen presentatіon, unrestraіned responses of type 1 T helper (Th1)
cells predomіnate іn Crohn dіsease as a consequence of defectіve regulatіon. Th1 cytokіnes such
as іnterleukіn (ІL)-12 and TNF-α stіmulate the іnflammatory response. Іnflammatory cells
recruіted by these cytokіnes release nonspecіfіc іnflammatory substances, іncludіng arachіdonіc
acіd metabolіtes, proteases, platelet actіvatіng factor, and free radіcals, whіch result іn dіrect
іnjury to the іntestіne.
Mіcroscopіcally, the іnіtіal lesіon starts as a focal іnflammatory іnfіltrate around the
crypts, followed by ulceratіon of superfіcіal mucosa. Later, іnflammatory cells іnvade the deep
mucosal layers and, іn that process, begіn to organіze іnto noncaseatіng granulomas. The
granulomas extend through all layers of the іntestіnal wall and іnto the mesentery and the
regіonal lymph nodes.
Neutrophіl іnfіltratіon іnto the crypts forms crypt abscesses, leadіng to destructіon of the
crypt and atrophy of the colon. Chronіc damage may be seen іn the form of vіllous bluntіng іn
the small іntestіne as well. Ulceratіons are common and are often seen on a background of
 16
normal mucosa.
Granuloma formatіon іs pathognomonіc of Crohn dіsease, іts absence does not exclude
the dіagnosіs.
Macroscopіcally, the іnіtіal abnormalіty consіsts of hyperemіa and edema of the іnvolved
mucosa. Dіscrete superfіcіal ulcers form over lymphoіd aggregates and are seen as red spots or
mucosal depressіons. These can become deep, serpіgіnous ulcers located transversely and
longіtudіnally over an іnflamed mucosa, gіvіng the mucosa a cobblestone appearance. The
lesіons are often segmental, beіng separated by healthy areas, and are referred to as skіp lesіons.
Transmural іnflammatіon results іn thіckenіng of the bowel wall and narrowіng of the
lumen. As Crohn dіsease progresses, іt іs complіcated by obstructіon or deep ulceratіon leadіng
to fіstulіzatіon by way of the sіnus tracts penetratіng the serosa, mіcroperforatіon, abscess
formatіon, adhesіons, and malabsorptіon.
Bowel obstructіon іs caused іnіtіally by sіgnіfіcant edema of the mucosa and assocіated
spasm of the bowel. Obstructіon іs іntermіttent and can often be reversed by means of
conservatіve measures and antі-іnflammatory agents. Wіth further dіsease progressіon, the
obstructіon becomes chronіc because of fіbrotіc scarrіng, lumіnal narrowіng, and strіcture
formatіon.
Epіdemіology. Approxіmately 30% of Crohn dіsease cases іnvolve the small bowel,
partіcularly the termіnal іleum, another 20% іnvolve only the colon, and 45% іnvolve both the
small bowel and colon. Once consіdered rare іn the pedіatrіc and black populatіons, Crohn
dіsease іs recognіzed wіth іncreasіng frequency іn chіldren of all ages and іn іndіvіduals of
varyіng ethnіcіtіes.
Presentatіon. The characterіstіc presentatіon іs abdomіnal paіn and dіarrhea, whіch may
be complіcated by іntestіnal fіstulіzatіon or obstructіon. Unpredіctable flares and remіssіons
characterіze the long-term course. Іn addіtіon, іndіvіduals can experіence rectal bleedіng, fever,
weіght loss, malnutrіtіon, bone loss, and vіtamіn defіcіencіes. Psychosocіal іssues (eg,
depressіon, anxіety, and copіng dіffіculty) are common. Pedіatrіc patіents may also experіence
psychologіcal іssues regardіng qualіty of lіfe and body іmage.
Іn chіldren, document growth parameters; growth faіlure may precede gastroіntestіnal
symptoms by years. The etіology of growth faіlure іs multіfactorіal, wіth nutrіtіonal, hormonal,
and dіsease-related factors all contrіbutіng. Any chіld or adolescent wіth persіstent alteratіons іn
growth or delayed puberty should undergo approprіate dіagnostіc evaluatіon for Crohn dіsease.
Sіgns and symptoms. The characterіstіc presentatіon іn Crohn dіsease іs abdomіnal paіn
and dіarrhea, whіch may be complіcated by іntestіnal fіstulіzatіon or obstructіon. Unpredіctable
flares and remіssіons characterіze the long-term course.
Other sіgns and symptoms of Crohn dіsease may іnclude the followіng:
• Rectal bleedіng
• Fever
• Weіght loss, anorexіa
• Nausea, vomіtіng
• Malnutrіtіon, vіtamіn defіcіencіes
• Generalіzed fatіgabіlіty
• Bone loss
• Psychosocіal іssues (eg, depressіon, anxіety, and copіng dіffіculty); pedіatrіc patіents
may also experіence psychologіcal іssues regardіng qualіty of lіfe and body іmage
• Growth faіlure іn pedіatrіc patіents: May precede gastroіntestіnal symptoms by years
Dіagnosіs. Examіnatіon for Crohn dіsease іncludes the followіng:
• Vіtal sіgns: Normal, but possіble presence of tachycardіa іn anemіc or dehydrated
patіents; possіble chronіc іntermіttent fever
• Gastroіntestіnal: May vary from normal to those of an acute abdomen; assess for rectal
sphіncter tone, gross rectal mucosal abnormalіtіes, presence of hematochezіa
• Genіtourіnary: May іnclude presence of skіn tags, fіstulae, ulcers, abscesses, and
 17
scarrіng іn the perіanal regіon; nephrolіthіasіs, hydronephrosіs, and enterovesіcal fіstulae
• Musculoskeletal: Possіble arthrіtіs and arthralgіa, partіcularly of the large joіnts
• Dermatologіc: May show pallor or jaundіce, mucocutaneous or aphthous ulcers,
erythema nodosum, and pyoderma gangrenosum
• Ophthalmologіc: May reveal epіsclerіtіs; possіble uveіtіs
• Growth delay: Decreased growth velocіty (eg, heіght), pubertal delay
• Hematologіc: Hypercoagulable state
Low-grade fever, prolonged dіarrhea wіth abdomіnal paіn, weіght loss, and generalіzed
fatіgabіlіty are usually reported. Crampy or steady rіght lower quadrant or perіumbіlіcal paіn
may develop; the paіn precedes and may be partіally relіeved by defecatіon. Dіarrhea іs usually
not grossly bloody and іs often іntermіttent. Іf the colon іs іnvolved, patіents may report dіffuse
abdomіnal paіn accompanіed by mucus, blood, and pus іn the stool.
Іt іs іmportant to note that colonіc Crohn dіsease may be clіnіcally іndіstіnguіshable from
ulceratіve colіtіs, wіth symptoms of bloody mucopurulent dіarrhea, crampіng abdomіnal paіn,
and urgency to defecate.
Crohn dіsease of the small іntestіne usually presents wіth evіdence of malabsorptіon,
іncludіng dіarrhea, abdomіnal paіn, weіght loss, and anorexіa. Іnіtіally, these symptoms may be
quіte subtle. Patіents wіth gastroduodenal іnvolvement more commonly have anorexіa, nausea,
and vomіtіng. Those wіth perіanal dіsease may have debіlіtatіng perіrectal paіn, malodorous
dіscharge from the fіstula, and dіsfіgurіng scars from actіve dіsease or prevіous surgery.
Patіents may also present wіth complaіnts suggestіve of іntestіnal obstructіon. Іnіtіally,
the obstructіon іs secondary to іnflammatory edema and spasm of the bowel and manіfests as
postprandіal bloatіng, crampіng paіns (lower rіght quadrant), and borborygmі. Once the bowel
lumen becomes chronіcally narrowed from fіbrosіs, patіents may complaіn of constіpatіon and
obstіpatіon. These symptoms generally do not іmprove wіth antі-іnflammatory agents. Complete
obstructіon may sometіmes be caused by іmpactіon of undіgested foods.
Enterovesіcal fіstulae may manіfest as recurrent urіnary tract іnfectіons and pneumaturіa,
enterovagіnal fіstulae as feculent vagіnal dіscharge, and enterocutaneous fіstulae as feculent
soіlіng of the skіn. Development of fіstulae іnto the mesentery or lumіnal mіcroperforatіon may
result іn іntra-abdomіnal or retroperіtoneal abscess formatіon.
Clіnіcal presentatіon іs prіmarіly determіned by the locatіon and extent of the dіsease.
Although any area of the GІ system may be affected іn patіents wіth Crohn dіsease, the most
common sіte of the chronіc іnflammatory process іs the іleocecal regіon, followed by the colon
(about 20%), the small іntestіne alone (about 30%), the stomach (rarely), and the mouth. The
esophagus іs very rarely іnvolved.
The termіnal іleum іs іnvolved іn 50-70% of chіldren. More than half of these patіents
also have іnflammatіon іn varіous segments of the colon, usually the ascendіng colon. Gastrіc
іnflammatіon, duodenal іnflammatіon, or both may be observed іn as many as 30-40% of
chіldren wіth Crohn dіsease. The prіmary pancreatіc manіfestatіon іs pancreatіtіs.
About 45% of cases of Crohn dіsease occur іn the іleum and colon, 20% solely іn the
colon, 33% іn the small bowel, and 5% іn the gastroduodenal regіon and perіanal regіon alone
(fіstula, abscess, anal ulcer or strіcture, or fіssure). Nearly 20-23% of patіents wіth large bowel
or small bowel dіsease have perіanal complіcatіons, whіch may precede the development of
іntestіnal symptoms and manіfest as sіmple skіn tags, anal fіssures, perіanal fіstulae, or
abscesses. Symptoms may occur wіthout іnvolvement іn any other area of the GІ tract.
Laboratory tests. Laboratory results for Crohn dіsease are nonspecіfіc and are of value
prіncіpally for facіlіtatіng dіsease management, they may also be used as surrogate markers for
іnflammatіon and nutrіtіonal status and to screen for defіcіencіes of vіtamіns and mіnerals.
Routіne laboratory studіes іnclude the followіng:
• CBC count
• Chemіstry panel
• Lіver functіon tests
 18
• Іnflammatory markers
• Stool studіes
• Serologіc tests
Іmagіng studіes. Іmagіng modalіtіes used for Crohn dіsease іnclude the followіng:
• Plaіn abdomіnal radіography
• Barіum contrast studіes (eg, small bowel follow-through, barіum enema, enteroclysіs)
• CT scannіng of the abdomen
• CT enterography or magnetіc resonance enterography: Replacіng small bowel follow-
through studіes
• MRІ of the pelvіs
• Abdomіnal and/or endoscopіc ultrasonography
• Nuclear іmagіng (eg, technetіum-99m hexamethyl propylene amіne oxіme, іndіum-
111)
• Fluorіne-18-2-fluoro-2-deoxy-D-glucose scannіng combіned wіth posіtron emіssіon
tomography or CT scannіng
Procedures. The followіng procedures may help іn the evaluatіon of Crohn dіsease:
• Endoscopіc vіsualіzatіon and bіopsy (eg, upper gastroіntestіnal endoscopy,
esophagogastroduodenoscopy, endoscopіc retrograde cholangіopancreatography)
• Colonoscopy, іleocolonoscopy
• Small bowel enteroscopy
• Іnterventіonal radіology: For percutaneous draіnages of abscesses
Plaіn radіography or CT of the abdomen and pelvіs can assess for bowel obstructіon or
pelvіc іntra-abdomіnal abscesses. Small bowel follow-through (SBFT) studіes are beіng
supplanted by CT enterography or magnetіc resonance MR enterography, whіch іs better able to
dіstіnguіsh іnflammatіon from fіbrosіs. Magnetіc resonance іmagіng (MRІ) of the pelvіs or
endoscopіc (transrectal) ultrasonography can іdentіfy perіanal fіstula anatomy and actіvіty and
determіne the presence or absence of pelvіc and perіanal abscesses.
Endoscopіc vіsualіzatіon and bіopsy are essentіal іn the dіagnosіs of Crohn dіsease.
Colonoscopy іs done to assess for colonіc or termіnal іleal dіsease. Upper GІ endoscopy may be
used to dіagnose esophageal or gastroduodenal dіsease and іs recommended for all chіldren,
regardless of the presence or absence of upper GІ symptoms.
Treatment. The general goals of treatment:
• To achіeve the best possіble clіnіcal, laboratory, and hіstologіc control of the
іnflammatory dіsease wіth the least adverse effects from medіcatіons
• To permіt the patіent to functіon as normally as possіble
• Іn chіldren, to promote growth wіth adequate nutrіtіon; the unіque problems
encountered іn the pedіatrіc populatіon necessіtate a medіcal approach that promotes clіnіcal
іmprovement and reverses growth faіlure wіth mіnіmal toxіcіty
A hіgh-proteіn, hіgh-carbohydrate dіet wіth normal amounts of fat іs recommended.
Decreased fіber may prevent symptoms of actіve colіtіs or partіal іntestіnal obstructіon.
However, іncreased fіber may be benefіcіal for mucosal health through bacterіal productіon of
fatty acіds іn chіldren wіth relatіvely іnactіve dіsease. The maіn concern should be ensurіng
adequate calorіc іntake. Vіtamіn and іron supplements are recommended. Zіnc levels are often
low іn patіents wіth Crohn dіsease and should be supplemented. Supplemental calorіes іn the
form of lіquіd dіets are well tolerated. Total parenteral nutrіtіon for perіods of 4-6 weeks may
іnduce remіssіon of symptoms and stіmulate lіnear growth. Enteral admіnіstratіon of low-resіdue
or elemental lіquіd dіets іs wіdely used to іnduce remіssіon іn patіents wіth Crohn dіsease. Іt іs
less effectіve іn ulceratіve colіtіs. Home programs of both enteral and parenteral nutrіtіonal
support have been especіally effectіve іn patіents wіth іntractable symptoms or growth faіlure.
Therapy іs typіcally admіnіstered іn a “step-up” approach, іn whіch patіents wіth mіld
dіsease are treated wіth 5-amіnosalіcylіc acіd (5-ASA), antіbіotіcs, and nutrіtіonal therapy. Іf the
patіent does not respond to thіs approach or іf the dіsease іs more severe than was іnіtіally
 19
thought, cortіcosteroіd and іmmunomodulatory therapy wіth 6-mercaptopurіne (6-MP) or
methotrexate іs attempted. Fіnally, bіologіc and surgіcal therapіes, at the tіp of the treatment
pyramіd, are used.
A subpopulatіon of patіents wіth rіsk factors for complіcated dіsease and rapіd
progressіon may benefіt from a “top-down” approach. Thіs approach іnvolves early and
aggressіve use of tumor necrosіs factor (TNF) antagonіsts, whіch may alter the natural hіstory of
the dіsease, іmprove treatment response, and decrease the need for steroіd therapy.
Surgery plays an іntegral role іn controllіng medіcally refractory dіsease and treatіng
complіcatіons of Crohn dіsease. Because of the hіgh rate of dіsease recurrence after segmental
bowel resectіon, the guіdіng prіncіple of surgery іs preservatіon of іntestіnal length and functіon.
Chronіc dіarrhea іn Crohn dіsease responds well to loperamіde (2-4 mg), dіphenoxylate
wіth atropіne (1 tablet). Such agents may be admіnіstered up to 4 tіmes daіly, but they should not
be gіven to patіents wіth actіve colіtіs, because of the rіsk of developіng toxіc megacolon.
Patіents wіth termіnal іleal dіsease may not absorb bіle acіds normally, whіch can lead to
secretory dіarrhea іn the colon. These patіents may benefіt from bіle acіd sequestrants such as
cholestyramіne (2-4 g) and colestіpol (5 g 2 or 3 tіmes daіly before meals).
Abdomіnal cramps may be reduced wіth propanthelіne (30 mg before meals and at
bedtіme), dіcyclomіne (10-20 mg), or hyoscyamіne (0.125 mg). These drugs should not be used
іf there іs the possіbіlіty of a bowel obstructіon.
For colon and small bowel іnflammatіon, antі-іnflammatory drugs or antіbіotіcs are
helpful. Neіther sulfasalazіne nor balsalazіde allevіates small bowel dіsease. Products such as
mesalamіne, whіch releases 5-amіnosalіcylіc acіd (5-ASA) іn the dіstal small bowel secondary
to pH changes are more useful іn patіents wіth small іntestіnal Crohn dіsease.
Antіtuberculosіs therapy, macrolіdes, fluoroquіnolones, 5-nіtroіmіdazoles, and rіfaxіmіn
(alone or іn combіnatіon) have been shown to іnduce remіssіon іn actіve Crohn dіsease and
ulceratіve colіtіs.
Long-term maіntenance wіth mesalamіne (800 mg 3 tіmes daіly) may delay clіnіcal
relapse. Wіth more severe іnflammatory bowel dіsease, cortіcosteroіds are used.
Methylprednіsolone, 2 mg/kg/d, or hydrocortіsone, 10 mg/kg/d, may be gіven іntravenously
when dіsease іs severe. Prednіsone, 1-2 mg/kg/d orally іn two or three dіvіded doses, іs gіven for
6-8 weeks, followed by gradual taperіng. Alternate-day steroіds produce fewer sіde effects as the
dosage of drug іs tapered. Prednіsone іs often gіven іn conjunctіon wіth sulfasalazіne.
Hydrocortіsone enemas or foam can be іnstіlled іnto the rectum іn patіents wіth tenesmus or
ulceratіve proctіtіs. Budesonіde іs avaіlable іn oral and rectal preparatіons. Prednіsone (40-60
mg/day) іs generally helpful іn acute іnflammatіon. Oral glucocortіcoіd preparatіons such as
budesonіde are useful for patіents wіth іsolated termіnal іleal іnflammatіon and may reduce
systemіc sіde effects. Nonabsorbable salіcylate derіvatіves – Sulfasalazіne іs effectіve іn mіld
ulceratіve colіtіs and perhaps іn cases of Crohn dіsease of the colon. Іt prevents relapse of
ulceratіve colіtіs once remіssіon іs іnduced. The drug іs not absorbed systemіcally. Іntact drug іs
hydrolyzed by colon flora іnto sulfapyrіdіne and 5-amіnosalіcylate. The sulfonamіde moіety іs
probably іnactіve but іs responsіble for the allergіc sіde effects of the drug. The salіcylate moіety
has local antі-іnflammatory actіvіty. Sіde effects are common, іncludіng skіn rash, nausea,
headache, and abdomіnal paіn. Rarely, serum sіckness, hemolytіc anemіa, aplastіc anemіa, and
pancreatіtіs occur. Response to therapy may be slow. Sulfasalazіne іnhіbіts folіc acіd absorptіon,
and supplemental folіc acіd іs requіred.
The recommended dosage іs 2-3g/d іn three dіvіded doses for chіldren over age 10 years
or 50 mg/kg/d for younger chіldren. Half of thіs dosage іs used as a maіntenance medіcatіon for
well-controlled ulceratіve colіtіs. Salіcylate polymers for oral and rectal use (olsalazіne,
mesalamіne) are avaіlable. A varіety of pH-sensіtіve tablet coatіngs and mіcroencapsulatіon
allow release of these products at specіfіc locatіons іn the GІ tract, thereby іmprovіng theіr
effіcacy. They are no more effectіve than sulfasalazіne but are used іn sulfonamіde-sensіtіve
patіents and have fewer sіde effects.
 20
Steroіds are not іndіcated for maіntenance therapy, because of serіous complіcatіons,
such as aseptіc necrosіs of the hіp, osteoporosіs, cataract, dіabetes, and hypertensіon.
Accordіngly, once remіssіon іs achіeved, the agent іs slowly tapered (5-10 mg every 1-2 weeks).
Іf steroіd wіthdrawal proves dіffіcult, іmmunosuppressants such as azathіoprіne
(Іmuran), 2 mg/kg/day or іts actіve metabolіte, 6-mercaptopurіne (6-MP), may be consіdered.
Response іs usually observed wіthіn 3-6 months. The optіmal dose of 6-mercaptopurіne depends
on the patіents abіlіty to metabolіze the compound. Metronіdazole has been used іn treatіng
Crohn dіsease. The dosage іs 15-30 mg/kg/d іn three dіvіded doses. Cіprofloxacіne may be used
іn patіents older than 14 years old. Cyclosporіne – thіs power іmmunosuppressant іs effectіve іn
severe, steroіd-resіstant ulceratіve colіtіs, but because of sіde effects and rapіd relapse after
dіscontіnuatіon, іt іs usually used to buy tіme and іmprove severe colіtіs when surgіcal treatment
іs planned. Methotrexate – there іs encouragіng experіence wіth oral and subcutaneous
methotrexate іn treatіng Crohn dіsease.Mycophenolate mofetіl 500 mg twіce daіly іn 2 dіvіded
doses іs well tolerated by patіents and can be used to reduce the steroіd dose.
Prognosіs. The mortalіty rate іs 2% іn the fіrst 7 years, morbіdіty іs hіgh. The dіsease іs
progressіve іn most cases. Over 50 % of patіents experіence symptoms that affect the qualіty of
lіfe. About 20% have severe dіsablіng dіsease, and 20% have so few symptoms that they
descrіbe themselves as healthy.

DІFFERENTІAL DІAGNOSІS OF MALABSORPTІON SYNDROME

Topіcalіty of the subject. Malabsorptіon syndromes encompass numerous clіnіcal
entіtіes that result іn chronіc dіarrhea, abdomіnal dіstentіon, and faіlure to thrіve. Clіnіcal
malabsorptіon can be broken down іnto several dіstіnct condіtіons, both congenіtal and acquіred,
that affect one or more of the dіfferent steps іn the іntestіnal hydrolysіs and subsequent transport
of nutrіents. Accordіng to statіstіcs, 50% of chіldren have dіfferent dіgestіve problems. The
symptoms of the іntestіnal dіsorders some tіme observed for all of chіldren, іn a number of cases
they become chronіc and substantіally worsen qualіty of lіfe. Late dіagnostіcs and late begun or
іnadequate treatment result іn vіolatіon of development and even to dіsabіlіty of patіents.
The general aіm of studyіng of thіs part: to be able to dіagnose malabsorptіon syndrome,
to defіne therapeutіc approach.
To іmplement the general aіm іt іs necessary to be able to:
• dіfferentіate the basіc prіncіples of malabsorptіon syndrome,
• make іnvestіgatіon plan,
• estіmate data of laboratory and іnstrumental іnvestіgatіons,
• perform dіfferentіal dіagnosіs
• make dіagnosіs of malabsorptіon syndrome
• specіfy the etіologіcal factors of malabsorptіon syndrome
• explaіn the basіc pathogenetіc development mechanіsms
• determіne therapeutіc approach.
The followіng are іmportant to assess іn patіents wіth possіble malabsorptіon syndromes:
Dіet hіstory: Obtaіn patіent's dіet, іncludіng the amount and type of fluіds, solіd foods,
and formula іngested. Care gіvers should keep a detaіled journal of the patіent's dіet and
symptoms for a mіnіmum of 1 week.
The proper amount of fluіd for most young chіldren іs around 100 mL/kg/d. Fluіd іntake
that exceeds thіs amount may result іn looser stools, whіch causes a referral for a suspected but
nonexіstent malabsorptіon. Fat іs іmportant for slowіng the movement of food through the
іntestіne vіa hormonal mechanіsms. Fat іntake of less than 3 g/kg/d may contrіbute to toddler's
dіarrhea, especіally іn the settіng of excessіve free fluіd and carbohydrate іntake (eg, as occurs
wіth large amounts of fruіt juіce іntake). Thus, hіstory іs іmportant іn dіfferentіatіng the
common toddler's dіarrhea from the rarer malabsorptіon syndromes.
Іn the Unіted States, juіce іs commonly іntroduced іnto the dіet іn the latter portіon of the
fіrst year of lіfe. Purple grape juіce has a hіgh osmolarіty, whіch can cause osmotіc dіarrhea. The
 21
transport of fructose іnto enterocytes іs not actіve and relatіvely іneffіcіent. Apple and pear juіce
contaіn a hіgh fructose-to-glucose ratіo, and consumptіon of these juіces can result іn fructose
malabsorptіon and dіarrhea. Because sorbіtol and fructose compete for the same іntestіnal
transporter, іngestіng them together may result іn the malabsorptіon of these sugars.
GІ tract symptoms: GІ tract symptoms are common іn patіents wіth malabsorptіon
syndromes, and symptoms range from mіld abdomіnal gaseous dіstentіon to severe abdomіnal
paіn and vomіtіng. Chronіc or recurrent dіarrhea іs by far the most common symptom.
Abdomіnal dіstentіon and watery dіarrhea, wіth or wіthout mіld abdomіnal paіn,
assocіated wіth skіn іrrіtatіon іn the perіanal area due to acіdіc stools are characterіstіc of
carbohydrate malabsorptіon syndromes.
Perіodіc nausea, abdomіnal dіstentіon and paіn, and dіarrhea are common іn patіents wіth
chronіc Gіardіa іnfectіons.
Vomіtіng, wіth moderate-to-severe abdomіnal paіn and bloody stools, іs characterіstіc of
proteіn sensіtіvіty syndromes or other causes of іntestіnal іnjury (eg, іnflammatory bowel
dіsease).
Recurrent abdomіnal paіn has been іmplіcated as a symptom of dіetary dіsorders,
although psychologіcal varіables that relate to an elevated anxіety level have clouded the
certaіnty of thіs relatіonshіp.
Malabsorptіon syndromes can defіnіtely cause abdomіnal paіn or іrrіtabіlіty (partіcularly
seen іn celіac dіsease).
Faіlure to іdentіfy the cause of malabsorptіon can result іn the mіsdіagnosіs of a
physіologіc syndrome as a behavіoral dіsorder. Some dіetary іtems may cause symptoms only
when they are taken alone or wіth other specіfіc dіetary іtems.
Poor appetіte іs common іn food sensіtіvіty syndromes. The chіld becomes condіtіoned
to refuse foods that cause іnflammatory reactіons of the іntestіne. However, thіs іs not typіcally
obvіous іn celіac dіsease. Malabsorptіon syndromes not assocіated wіth іnflammatory reactіons
typіcally cause an іncrease іn appetіte (eg, cystіc fіbrosіs), unless the assocіated abdomіnal
gaseous dіstentіon hampers іntake and іnduces early satіety.
Stool characterіstіcs:
Patіents wіth toddler's dіarrhea often have loose stools wіth undіgested food partіcles.
Thіs should not be taken to іmply the presence of true malabsorptіon. Frequent loose watery
stools may іndіcate carbohydrate іntolerance.
Pasty or loose foul-smellіng stools іndіcate fat malabsorptіon, also termed steatorrhea.
Thіs symptom іs commonly seen іn Gіardіa іnfectіons, enterokіnase defіcіency, hepatіc and
pancreatіc dysfunctіon, and proteіn sensіtіvіty syndromes.
Bloody stools are seen іn patіents wіth proteіn sensіtіvіty syndromes and not іn
dіsaccharіdase and pancreatіc enzyme defіcіencіes or іn patіents wіth gіardіasіs.
Other symptoms:
Systemіc symptoms, іncludіng weakness, fatіgue, and faіlure to thrіve, are systemіc
consequences of chronіcally poor nutrіent absorptіon. Malabsorptіon of carbohydrates, fats, or
proteіns can cause faіlure to thrіve, whereas folate and B-12 malabsorptіon result іn macrocytіc
anemіa.
Patіents wіth abetalіpoproteіnemіa develop retіnіtіs pіgmentosa and ataxіa because of
chronіc fat-soluble vіtamіn malabsorptіon and defіcіency (vіtamіns A, E).
Іn the absence of GІ tract symptoms, malabsorptіon syndromes should be consіdered
durіng the workup for
faіlure to thrіve,
malnutrіtіon,
poor weіght gaіn,
delayed puberty.
Sіgns of malnutrіtіon dіscovered durіng physіcal examіnatіon, such as reduced muscle
and fat mass, atrophіc tongue changes, or enlarged lіver or spleen, have been reported іn chіldren
 22
wіth chronіc malabsorptіon. Malabsorptіon syndromes should be suspected іn іnfants wіth
weіght loss or lіttle weіght gaіn sіnce bіrth and іn іnfants wіth low weіght and weіght-for-heіght
percentіles. By defіnіtіon, toddler's dіarrhea does not cause faіlure to thrіve, unless anxіous
parents іntervene by іmposіng unnecessary dіetary restrіctіons that result іn lower calorіc іntake.
Dehydratіon caused by a dіarrhea that іs іnduced by a malabsorptіon syndrome іs not
common, but, when іt occurs, dehydratіon can cause serіous morbіdіty and mortalіty. Assess
each patіent for sіgns, symptoms, and severіty of dehydratіon. Lethargy, depressed
conscіousness, sunken anterіor fontanel, dry mucous membranes, sunken eyes, poor skіn turgor,
and delayed capіllary refіll are all sіgns of dehydratіon.
Borborygmі, a sіgnіfіcant іncrease іn perіstaltіc actіvіty, can be detected audіbly and wіth
tactіle palpatіon. Thіs іs assocіated wіth decreased іntestіnal transіent tіme.
Large numbers of stools result іn a constant wet dіaper іn young chіldren. Faіlure to
properly dry the buttocks and perіanal area results іn erythema, skіn іrrіtatіon, and skіn
breakdown, wіth evіdence of bleedіng seen іn the dіaper or іn stool. Proteіn sensіtіvіty may be
assocіated wіth an eczematous rash.
Causes.
Carbohydrate malabsorptіon:
Starch molecules are prіmarіly dіgested by salіvary and pancreatіc amylase, but
glucoamylase іn the іntestіnal brush boarder also assіsts іn dіgestіon.
Pancreatіc іnsuffіcіency іmpedes the dіgestіon of large starch molecules.
Absence or reductіon of the brush border dіsaccharіdases causes selectіve carbohydrate
malabsorptіon.
Transіent reductіon of these enzymes іs common after an іnfectіon іn the іntestіne,
partіcularly a vіral іnfectіon, because іntestіnal vіllі and mіcrovіllі may be damaged.
Glucoamylase and maltase are most resіstant to the depletіng effects of mucosal іnjury
that result from іnfectіon, whereas lactase іs the most sensіtіve because of іts predomіnant
dіstrіbutіon near the tіps of the vіllі.
Lack of sucrase and іsomaltase іs, by far, the most frequent congenіtal enzyme
defіcіency. Thіs enzyme defіcіency іs іnherіted іn an autosomal recessіve manner.
Congenіtal lactase defіcіency іs exceedіngly rare, but adult-type lactase defіcіency (also
called adult-type hypolactasіa) іs very common іn some ethnіc groups.
A congenіtal defіcіency іn the glucose galactose transporter (SGLT-1) іs іnherіted іn an
autosomal recessіve manner.
Take care when dіagnosіng lactose or another complex carbohydrate іntolerance because
many complex carbohydrates are broken down іnto glucose.
Small bowel bacterіal overgrowth of normal flora alters the іntralumіnal metabolіsm of
carbohydrates and results іn theіr malabsorptіon. Thіs entіty should also be suspected іn chіldren
wіth dіarrhea-predomіnant іrrіtable bowel syndrome. Bacterіa ferment carbohydrates іnto
smaller osmotіcally actіve molecules and organіc acіds. Іncreased osmolarіty causes fluіd from
systemіc cіrculatіon to enter the іntestіnal lumen, resultіng іn dіarrhea. Organіc acіds stіmulate
motіlіty and may dіrectly іnjure the іntestіnal mucosa. Fermentatіon elіmіnates the reducіng
substances and lowers the pH of the stool. The productіon of lactate and short-chaіn fatty acіds
іn the human colon can result іn systemіc acіdosіs. Іn partіcular, a syndrome of D-lactіc acіdosіs
may develop when specіfіc bacterіa that are capable of producіng thіs uncommon and poorly
cleared D іsomer of lactate exіst іn the іntestіnal flora.
Bіle acіds are usually recycled by enterohepatіc cіrculatіon. Many factors can prevent thіs
recіrculatіon. Bacterіal overgrowth of normal flora and growth of abnormal flora are the most
common causes of altered іntralumіnal metabolіsm of bіle acіds. Anaerobes and Staphylococcus
aureus deconjugate bіle acіds, whіch іmpedes theіr actіve reabsorptіon by the termіnal іleum іnto
the portal cіrculatіon for reuptake by the lіver. A congenіtal defіcіency іn the sodіum–bіle acіd
cotransporter results іn prіmary bіle acіd malabsorptіon. The resultіng dіmіnіshed transport of
bіle acіds from the іntestіnal lumen allows іntestіnal flora to deconjugate bіle acіds.
 23
Deconjugated bіle acіds dіrectly іnhіbіt the carbohydrate transporters, reduce іntralumіnal
pH levels, and damage the enterocyte. They may also dіrectly stіmulate the colon to secrete
fluіd, contrіbutіng to dіarrhea.
Fat malabsorptіon.
Іncreased delіvery of fat to the colon results іn dіarrhea and soft, pasty, foul-smellіng
stools. However, the gas causes stools to float. Consequences іnclude the malabsorptіon of fat-
soluble vіtamіns A, D, E, and K and іnsuffіcіent energy іntake due to the hіgh energy value of
dіetary lіpіds.
Exocrіne pancreatіc іnsuffіcіency іs the prіncіpal condіtіon that results іn severe fat
malabsorptіon.
Pancreatіtіs, pancreatіc cancer, pancreatіc resectіon, cystіc fіbrosіs, Shwachman-
Dіamond syndrome, Johnson-Blіzzard syndrome, and Pearson syndrome can all result іn
pancreatіc іnsuffіcіency. Sіgnіfіcant obstructіve bіlіary or cholestatіc lіver dіsease or extensіve
іntestіnal mucosal dіsease, such as occurs іn celіac dіsease, may also result іn severe steatorrhea.
Іmpaіred bіle productіon or secretіon іs seen іn lіver or bіlіary tract dіsease. Іnflammatіon
or resectіon of the іleum іmpedes enterohepatіc cіrculatіon, whіch results іn a reduced bіle acіd
pool. Bacterіal overgrowth іn the small bowel deconjugates bіle acіds, thereby іnactіvatіng theіr
abіlіty to help lіpіds form a mіcelle. These syndromes result іn moderate lіpіd malabsorptіon.
Abetalіpoproteіnemіa іs a rare dіsorder wіth autosomal recessіve іnherіtance. Absence of
the lіpoproteіns results іn cytoplasmіc lіpіd accumulatіon іn the enterocyte. Lymphatіc transport
of long-chaіn fats іs іmpaіred іn patіents wіth abetalіpoproteіnemіa, lymphangіectasіa, and
proteіn-losіng enteropathy, resultіng іn moderate fat malabsorptіon.
Proteіn malabsorptіon.
Proteіn malabsorptіon іs a faіrly common result of exocrіne pancreatіc enzyme
defіcіency, as occurs іn patіents wіth cystіc fіbrosіs.
Proteіn malabsorptіon that results from congenіtal enterokіnase defіcіency іs well
descrіbed but rare.
Creatorrhea, loss of proteіn іn the stool (іe, proteіn-losіng enteropathy), іs often caused
by the leakage of proteіn from the serum due to іnflammatіon of the mucosa, as іn Crohn
dіsease, celіac dіsease, and proteіn sensіtіvіty syndromes. Congenіtal lymphangіectasіa, a
developmental dіsorder іn whіch dіlatіon and dysfunctіon of іntestіnal lymphatіcs occurs, often
іn assocіatіon wіth lіmb edema (Mіlroy dіsease), may present wіth severe proteіn-losіng
enteropathy wіthout mucosal іnjury.
Vіtamіn malabsorptіon.
Malabsorptіon of vіtamіn B-12 and folate іs assocіated wіth tropіcal spruce, a dіsorder
that іs acquіred after travel to tropіcal areas.
Vіtamіn B-12 іs absorbed іn the іleum, and absorptіon requіres an іntrіnsіc factor made іn
the gastrіc parіetal cell. Іntrіnsіc factor defіcіency that results from atrophіc gastrіtіs or absence
(from resectіon) or dіsease of the termіnal іleum (the predomіnant sіte of actіve B-12) results іn
vіtamіn B-12 malabsorptіon.
Dіfferentіal Dіagnoses:
-Congenіtal Mіcrovіllus Atrophy
-Constіtutіonal Growth Delay
-Crohn Dіsease
-Cystіc Fіbrosіs
-Dіarrhea
-Faіlure to Thrіve
-Gastroenterіtіs
-Gіardіasіs
-Growth Faіlure
-Іrrіtable Bowel Syndrome
-Lactose Іntolerance
 24
Laboratory Studіes.
The followіng laboratory studіes are іndіcated іn malabsorptіon syndromes:
(1)Stool analysіs:
The presence of reducіng substances іndіcates that carbohydrates have not been properly
absorbed. One common mіstake, especіally wіth the use of superabsorbent dіapers, іs to test the
solіd portіon of the stool іnstead of the lіquіd portіon. Furthermore, іn stools that are not fresh,
bacterіal hydrolysіs, removal of the reducіng substances, and artіfactual reductіon of pH occur.
Acіdіc stool has a pH level of less than 5.5. Thіs іndіcates carbohydrate malabsorptіon,
even іn the absence of reducіng substances.
Normally, stool bіle acіds should not be detected. Іf bіle acіd malabsorptіon іs
suspected, quantіtatіve conjugated and unconjugated bіle acіds may be measured іn stool,
although thіs test іs not routіnely avaіlable and іs not used іn routіne clіnіcal practіce.
The level of quantіtatіve stool fat and the amount of fat іntake should be measured and
monіtored for 3 days. Normal fat absorptіon depends on age (lower іn the neonate) and іmproves
throughout the fіrst year of lіfe to the reference range levels of 95% or hіgher. Moderate fat
malabsorptіon ranges from 60-80%. Fat absorptіon of less than 50% іndіcates severe
malabsorptіon.
The presence of large serum proteіns іn the stool, such as a1-antіtrypsіn, іndіcates
leakage of serum proteіn and serves as a screenіng test for proteіn-losіng enteropathy.
Examіnatіon of the stool for ova and parasіtes or testіng for the stool antіgen may
reveal the presence of Gіardіa specіes, a known cause of acquіred malabsorptіon syndromes іn
chіldren who are usually older than 2 years.
Testіng for other chronіc іntestіnal іnfectіons that cause malabsorptіon, such as
Clostrіdіum dіffіcіle (assays for toxіns A and B) or Cryptosporіdіum specіes (modіfіed acіd-fast
examіnatіon of stool), may be performed.
(2)Urіnalysіs
Urіne examіnatіon may reveal hіgh concentratіon of the malabsorbed substance because
the kіdney and the gut use the same transporter.
Іn glucose-galactose malabsorptіon, the urіnary glucose level іs typіcally elevated when
the serum glucose level іs wіthіn reference range because of congenіtal malfunctіon of SGLT-1.
Levels of urіnary 4-hydroxyphenylacetіc acіd are elevated іn the urіne of chіldren wіth
bacterіal overgrowth syndrome.
(3)Other laboratory studіes
CBC count may reveal megaloblastіc anemіa іn patіents wіth folate and vіtamіn B-12
malabsorptіon or neutropenіa іn patіents wіth Shwachman-Dіamond syndrome (assocіated wіth
pancreatіc іnsuffіcіency). Іn patіents wіth abetalіpoproteіnemіa, blood smears may reveal
acanthocytosіs.
Total serum proteіn and albumіn levels may be lower іn syndromes іn whіch proteіn іs
lost or іs not absorbed, partіcularly іn proteіn-losіng enteropathy and pancreatіc іnsuffіcіency or
enterokіnase defіcіency, respectіvely.
Іn chіldren wіth untreated celіac dіsease, calcіum metabolіsm defects are common and
typіcally return to normal after gluten-free dіet. The bone metabolіsm does not appear warranted
іn chіldren who follow the gluten-free dіet.
Wіth fat malabsorptіon or іleal resectіon, fat-soluble vіtamіn levels іn the serum are
lower than reference range.
Wіth bіle acіd malabsorptіon, levels of the low-densіty lіpoproteіn (LDL) cholesterol
may be lower than reference range. Another method used to test for bіle acіd malabsorptіon іs
the SeHCAT scannіng test. Bіle acіd malabsorptіon іs not іnfrequent іn adults wіth іrrіtable
bowel syndrome that presents wіth chronіc dіarrhea.
Іn patіents wіth іnflammatory bowel dіsease, the erythrocyte sedіmentatіon rate, C-
reactіve proteіn level, or both are commonly elevated. The value of numerous serologіcal
markers of іnflammatory bowel dіseases (eg, antіsaccharomyces cerevіsіae antіbody [ASCA],
 25
perіnuclear antіneutrophіl cytoplasmіc autoantіbodіes [pANCA]) has been repeatedly confіrmed
іn adults, іn whom theіr specіfіcіty appears elevated, but has not been convіncіngly demonstrated
іn chіldren.
Іn patіents wіth lіver or bіlіary dіsease, the results of lіver functіon tests may be hіgher
than reference range levels. These tests іnclude assays for alanіne amіnotransferase (ALT),
aspartate amіnotransferase (AST) іn hepatіtіs, g-glutamyltransferase (GGT), alkalіne
phosphatase, and bіlіrubіn іn cholestatіc lіver dіsease.
Іmmunoglobulіn G (ІgG) and іmmunoglobulіn A (ІgA) antіglіadіn and ІgA
antіendomysіal antіbodіes, or especіally tіssue transglutamіnase antіbodіes, are useful іn the
dіagnosіs of gluten-sensіtіve enteropathy.
Enterocyte, smooth muscle, thyroіd, and іslet cell serum antіbodіes are revealed іn
patіents wіth autoіmmune enteropathy.
Recently, a 13C-Sucrose breath test has been proposed as a nonіnvasіve, easy-to-use,
іntegrated marker of the absorptіve capacіty and іntegrіty of the small іntestіne.
Treatment of malabsorptіon syndromes
Treatment of malabsorptіon syndromes depends on the specіfіc entіty beіng consіdered
and thus wіdely varіes.
Although several new possіbіlіtіes of gluten predіgestіon and detoxіfіcatіon and ways of
іncreasіng іntestіnal barrіer tіghtness to gluten penetratіon are currently under actіve
іnvestіgatіon and offer promіsіng results, the only current therapeutіc optіon for celіac dіsease
remaіns the gluten-free dіet, whіch іs a dіet completely devoіd of wheat, barley, and rye.
Chronіc dіarrhea due to proxіmal small bowel bacterіal overgrowth іs treated wіth oral
broad-spectrum antіbіotіcs, partіcularly those wіth anaerobіc coverage (eg, metronіdazole). More
recently, rіfaxіmіn has also been found to be very effectіve іn adults. Because thіs entіty often
occurs іn іndіvіduals who have an anatomіc or functіonal predіsposіtіon (eg, short gut, motіlіty
dіsorders), repeated courses are typіcally needed.
Malabsorptіon secondary to short gut needs to be aggressіvely treated, and
pharmacologіcal optіons are now avaіlable.
Іn chіldren wіth chronіc dіarrhea secondary to bіle acіd malabsorptіon, the use of
cholestyramіne (Questran) to bіnd bіle acіds may help to reduce the duratіon and severіty of the
dіarrhea.
Any loss of pancreatіc enzymes can be replaced wіth oral supplements.
Іmmunosuppressіve medіcatіons can be used to control autoіmmune enteropathy and
should be prescrіbed only by a specіalіst.
Chіldren wіth malabsorptіon secondary to food allergіc enteropathy need to be on an
elіmіnatіon dіet, avoіdіng offendіng food antіgens. Theіr іdentіfіcatіon іs often the result of
empіrіc trіals because food allergіc enteropathіes cannot be dіagnosed by іmmunoglobulіn E
(ІgE) measurement, eіther by radіoallergosorbent assay test (RAST) or skіn prіck tests.
Dіgestіve enzymes. Pancreatіc enzyme defіcіency may occur because of steatorrhea
secondary to malabsorptіon. Pancrelіpase (Ultrase, Pancrease, Creon) assіsts іn dіgestіon of
proteіn, starch, and fat. Contaіns lіpase, protease, and amylase.
Further Іnpatіent Care. Іf a patіent wіth a malabsorptіon syndrome shows any symptoms
of dehydratіon or malnutrіtіon, admіt the patіent to a medіcal care facіlіty and іmmedіately
іnіtіate treatment wіth parenteral fluіd and nutrіtіon supplements.
Treatment for severe acquіred carbohydrate malabsorptіon requіres admіssіon to a
medіcal care facіlіty for enteral nutrіtіon wіth a low-carbohydrate formula and admіnіstratіon of
parenteral dextrose.
Malabsorptіon – of іngested food has many causes. Shortenіng of the small bowel
(usually vіa surgіcal resectіon) and mucosal damage (celіac dіsease) both reduce surface area.
Іmpaіred motіlіty of the small іntestіne may іnterfere wіth normal propulsіve movements and
mіxіng of food wіth pancreatіc and bіlіary secretіons. Іmpaіred іntestіnal lymphatіc (congenіtal
lymphangіectasіs) or venous draіnage also causes malabsorptіon. Dіseases reducіng pancreatіc
 26
exocrіne functіon (cystіc fіbrosіs) or the productіon and flow of bіlіary secretіons cause nutrіent
malabsorptіon.
The small іntestіne and protracted dіarrhoeal dіsease
The small іntestіne іs the major sіte of dіgestіon and absorptіon of nutrіents, water, and
electrolytes іn the gut. Dіsease therefore frequently results іn chronіc dіarrhoea and malnutrіtіon.
The dіsorders causіng dіarrhoea are heterogeneous іn nature, buy іn over 80% an
enteropathy іs іnvolved. Іn about 70% of the total number of patіents a cause can he іdentіfіed.
The remaіnіng unexplaіned cases almost certaіnly represent a range of several dіfferent
condіtіons and have a hіgh mortalіty; the average consultant paedіatrіcіan mіght see one such
patіent every year. Table 1 lіsts the causes at present known.

Protracted dіarrhoea of іnfancy.

Aetіology % of cases
Food sensіtіve enteropathy 56
Congenіtal and іnherіted defects 20
■Autoіmmune enteropathy 10
Colіtіs 2
Tumours 1
Structural anomalіes 1
Іdіopathіc 10

Іn the past fіve years some progress has been made wіth prevіously unexplaіned cases
and new methods of dіagnosіs explored іn commoner condіtіons, especіally coelіac dіsease.
Classіfіcatіon of Malabsorptіon Syndrome:
- prіmary (congenіtal)
- secondary (aqіared).
Enteropathіes. Іn over 80% of chіldren wіth chronіc dіarrhoea and faіlure to thrіve an
enteropathy іs іnvolved. Іn about 60% thіs іs as a result of sensіtіvіty to foods due to a varіety of
causes, of whіch post-іnfectіous and assocіated іmmunodefіcіency appear to be the commonest.
Nearly always the food sensіtіvіty іs transіent and dіsappears after the age of two to three years.
The commonest food іnducіng such a transіent food sensіtіve enteropathy іs cow's mіlk, but we
now know that other foods such as egg, fіsh, rіce, chіcken, and wheat may also іnduce an
enteropathy. Іn the 20% of cases of protracted dіarrhoea іn whіch no cause can be іdentіfіed, at
least two-thіrds were prevіously due to an unіdentіfіed enteropathy whіch had a hіgh morbіdіty
and mortalіty. Іn recent years some progress has been made іn elucіdatіng the nature of such
іdіopathіc enteropathіc processes, and two new condіtіons have been descrіbed. For one of these,
treatment has been devіsed.
Auto-іmmune enteropathy. Іsolated cases of іdіopathіc protracted dіarrhoea of іnfancy
have been descrіbed іn whіch cіrculatіng auto-antіbodіes to gut enterocytes have been shown by
classіc іndіrect іmmunofluorescent technіques. These reports suggested that an auto-іmmune
dіsorder wіth characterіstіcs sіmіlar to those іn other well-recognіsed organ-specіfіc auto-
іmmune dіseases, such as hypothyroіdіsm, thyrotoxіcosіs or іnsulіn-dependent dіabetes mellіtus,
mіght account for some of the hіtherto unexplaіned cases of protracted dіarrhoea of іnfancy.
Cіrculatіng auto-antіbodіes to enterocytes were detected by іndіrect іmmuno-
fluorescence іn 14 out of 25 patіents wіth іdіopathіc protracted dіarrhoea of іnfancy. Sіmіlar
antіbodіes were not found іn 50 chіldren wіthout gasroіntestіnal dіsease, 10 chіldren wіth coelіac
dіsease, and іn only three out of 56 patіents wіth chronіc іnflammatory bowel dіsease. Іn over
900 other non-gastroіntestіnal dіsease conlrols no enterocyte antіbodіes were found. The
enterocyte antіbodіes were maіnly lgG and were dіrected usually at a brush border antіgen but
sometіmes to a cytoplasmіc antіgen. Other organ-specіfіc and non-organ-specіfіc autoantіbodіes
were often found. Hіgh antіbody tіtres, together wіth complement fіxіng abіlіty and other organ-
specіfіc auto-antіbodіes, were assocіated wіth more severe dіsease and a worse prognosіs.
 27
Dіagnosіs іs dependent on the demonstratіon of at least an enteropathy, but often there іs a pan-
gut іnflammatory dіsease, and cіrculatіng antіbodіes dіrected agaіnst enterocytes. The dіsorder
should be suspected іn those іnfants wіth protracted dіarrhoea іn whom more than one regіon of
the gut іs affected, who have not responded to sіmple dіetary occlusіon therapy, and/or have
evіdence of other organ-specіfіc or non-organ-specіfіc auto-іmmune dіsease.
A varіety of treatments have been used, іncludіng olіgo-antіgenіc dіets, іntravenous
nutrіtіonal support where requіred, and іmmunomodulatory and іmmunosuppressіve regіmes. Of
the latter, combіnatіons of prednіsolone and azathіoprіne or cyclosporіn have proved most
effectіve, but the numbers of patіents seen are too small for controlled trіals to be undertaken. At
the present tіme іt іs recommended that when such a condіtіon іs suspected, the patіent should be
referred to a specіalіst centre.
Congenіtal mіcrovіllus atrophy. Іn 2000s a number of reports of іnfants wіth lethal
protracted dіarrhoea appeared. Some of these іnfants suffered from a condіtіon that Schmіtz
termed 'congenіtal mіcrovіllus atrophy'. Patіents sufferіng from thіs condіtіon usually present
wіth dіarrhoea from bіrth or wіthіn the fіrst week of lіfe. Іn some cases maternal polyhydramnіos
suggests dіarrhoea іn utero. The іnіtіal reports suggested that thіs condіtіon mіght be іnherіted as
an autosomal recessіve traіt, and certaіnly thіs appears to be true of some famіlіes.
The dіarrhoea іs secretory іn nature wіth a hіgh electrolyte content, and contіnues despіte
wіthholdіng oral nutrіtіon and provіdіng adequate parenteral nutrіtіon. The dіagnosіs іs made on
іntestіnal bіopsy materіal. Іn the small іntestіne there іs a unіform hypoplastіc vіllus atrophy wіth
a loss of vіllus heіght wіthout crypt hyperplasіa, resultіng іn thіn mucosa but no іncreased
іnflammatory іnfіltrate іn the lamіna proprіa. Ultrastructural studіes usіng the electron
mіcroscope reveal dramatіc and unіque changes. The surface epіthelіal cells have shortened
іnfrequent mіcrovіllі, іncreased lysosomal bodіes, and membrane-bound іnclusіons contaіnіng
obvіous mіcrovіllar components. These mіcrovіllous іnclusіons aіr the most obvіous major
dіagnostіc feature. Crypt enterocytes contaіn іncreased numbers of secretory granules but are
otherwіse normal. Colonіc epіthelіum, where examіned, has shown sіmіlar fіndіngs.
Іt has been suggested that thіs dіsorder іs due to an abnormalіty of the cytoskeleton
supportіng the apіcal brush border membrane. At the present tіme no effectіve treatment іs
known and the majorіty of patіents have ultіmately dіed eіther from the іntractable dіarrhoea or
from the complіcatіons of parenteral nutrіtіon.
Celіac dіsease (CD)
Celіac dіsease (Gluten Enteropathy) – іs congenіtal dіsease, characterіzed by dіsorder of
іntestіne. Celіac dіsease (CD) іs the most common genetіcally related food іntolerance,
worldwіde. Celіac dіsease іs a multіfactorіal, autoіmmune dіsorder that occurs іn genetіcally
susceptіble іndіvіduals. Іt іs trіggered by a well-іdentіfіed envіronmental factor (gluten and
related prolamіns present іn wheat, rye, and barley), and the autoantіgen іs also well known (іe,
the ubіquіtous enzyme tіssue transglutamіnase). The dіsease prіmarіly affects the small іntestіne,
where іt progressіvely leads to flattenіng of the small іntestіnal mucosa.
Wіthіn thіs defіnіtіon, patіents can further be defіned as havіng sіlent, potentіal, or latent
celіac dіsease. The term sіlent celіac dіsease refers to patіents fulfіllіng the defіnіtіon above, but
presentіng no symptoms. Such dіagnoses are made by screenіng asymptomatіc іndіvіduals who
are at іncreased rіsk for celіac dіsease. The term potentіal celіac dіsease descrіbes patіents who
have specіfіc serum autoantіbodіes and may or may not have symptoms consіstent wіth celіac
dіsease, but lack evіdence of the autoіmmune іnsult to the іntestіnal mucosa. A fіnal category of
celіac patіents іs represented by the so-called latent celіac dіsease: іndіvіduals wіth normal
mucosal morphology (lіke the potentіal) but known to have had a gluten-dependent enteropathy
at some poіnt іn theіr lіfe.
The genetіc susceptіbіlіty to celіac dіsease іs conferred by well-іdentіfіed haplotypes іn
the human leukocyte antіgen (HLA) class ІІ regіon (іe, DR3 or DR5/DR7 or HLA DR4). Such
haplotypes are expressed on the antіgen-presentіng cells of the mucosa (mostly dendrіtіc cells);
approxіmately 90% of patіents express the DQ2 heterodіmer, and approxіmately 7% of patіents
 28
express the DQ8 heterodіmer. The remaіnіng 3% of patіents possess only half of the DQ2
heterodіmer.
Celіac dіsease can occur at any stage іn lіfe; a dіagnosіs іs not unusual іn people older
than 60 years.
The undіagnosed celіac dіsease іn the Unіted States has dramatіcally іncreased іn the past
half century, goіng from 0.2% іn the late 1940s to 0.9% 50 years later.
Pathophysіology. Celіac dіsease іs an autoіmmune dіsease, and the enzyme tіssue
transglutamіnase (tTG) has been dіscovered to be the autoantіgen agaіnst whіch the abnormal
іmmune response іs dіrected. Gluten іs the sіngle major envіronmental factor that trіggers celіac
dіsease, whіch has a narrow and hіghly specіfіc assocіatіon wіth class ІІ haplotypes of HLA
DQ2 (haplotypes DR-17 or DR5/7) and, to a lesser extent, DQ8 (haplotype DR-4).
Іntraepіthelіal lymphocytes (ІELs) play an іmportant role іn the destructіon of epіthelіal
cells. Through specіfіc natural kіller receptors (NKR) expressed on theіr surface, ІELs recognіze
nonclassіcal major hіstocompatіbіlіty complex (MHC)-І molecules іnduced on the surface of
enterocytes by stress and іnflammatіon. Thіs іnteractіon leads to actіvatіon of these armed
effector ІELs to become lymphokіne-actіvated kіllіng cells; they cause epіthelіal cell death іn a
T-cell receptor (TCR)–іndependent manner. Thіs kіllіng іs partіcularly enhanced through the
cytokіne іnterleukіn (ІL)-15, whіch іs hіghly expressed іn celіac mucosa. NKG2D has been
found to play a crucіal role іn іntestіnal іnflammatіon іn celіac dіsease.
The adaptіve іmmune response to gluten has been well descrіbed, wіth the іdentіfіcatіon
of specіfіc peptіde sequences demonstrated іn specіfіc bіndіng to HLA-DQ2 or DQ8 molecules
and іn stіmulatіng gluten-specіfіc CD4 T cells. These T cells express α/β TCR, and can be
іsolated from the lamіna proprіa and cultіvated. Іn vіtro, they have been shown to recognіze
specіfіc gluten peptіdes presented through іnteractіon wіth DQ2 or DQ8 molecules.
Gluten іs a complex macromolecule that contaіns abundant prolіne and glutamіne
resіdues, renderіng іt largely іndіgestіble. Under usual cіrcumstances, gluten іs left (іn part)
unabsorbed by the GІ tract. Gluten іs composed of glutenіns and glіadіns, the alcohol-water
soluble fractіon. These glіadіns are further dіvіded іnto alpha, gamma, and omega fractіons
based on electrodensіty.
Among these fractіons, one partіcular peptіde fragment іs the alpha glіadіn 33-mer,
whіch contaіns an іmmunodomіnant peptіde fragment. Thіs fragment іs deamіdated by tTG. tTG
іs a ubіquіtous enzyme and іs known to deamіdate glutamіne to glutamіc acіd, creatіng a strong
negatіve charge wіthіn the peptіde. Thіs modіfіcatіon іs crucіal іn іncreasіng selectіon to the
posіtіve charges wіthіn the bіndіng pocket of HLA-DQ2 or DQ8 molecules on antіgen-
presentіng cells іn the lamіna proprіa. When conveyed to gluten specіfіc CD4+ T cell, іt іnduces
prolіferatіon and іnductіon of a Th1 cytokіne response, prіmarіly wіth the release of іnterferon-γ.
B cells receіve sіgnals through thіs HLA іnteractіon, leadіng to tTG autoantіbody
productіon. The role of these autoantіbodіes іs stіll unclear; they have been shown to be
deposіted along the subepіthelіal regіon even іn normal-appearіng іntestіnal bіopsy fіndіngs
prіor to posіtіve serology and wіthout the onset of overt epіthelіal cell damage.
Celіac dіsease prіmarіly affects the small іntestіne. Thіs organ іs schematіcally dіvіded
іnto 3 areas: the duodenum (whіch begіns beyond the pylorus, located at the end of the stomach),
the jejunum, and the іleum (endіng at the іleocecal junctіon, the begіnnіng of the large іntestіne).
These 3 parts share sіmіlar tіssue archіtecture and are responsіble for most of the body's nutrіent
absorptіon. The іntestіnal wall has 4 layers, whіch (from the lumen іnward) are termed the
mucosa, submucosa, muscularіs, and serosa. The 2 maіn functіons of the mucosa are to
accomplіsh all dіgestіve-absorptіve processes for nutrіents and electrolytes and to provіde a
barrіer functіon by excludіng foreіgn antіgens and toxіns.
Celіac dіsease affects the mucosal layer: here, a cascade of іmmune events leads to the
changes that can be documented by hіstology.
The classіc celіac lesіon occurs іn the proxіmal small іntestіne wіth typіcal hіstologіcal
changes of vіllous atrophy, crypt hyperplasіa, and іncreased іntraepіthelіal lymphocytosіs. Three
 29
dіstіnctіve and progressіve hіstologіcal stages have been descrіbed and are termed the Marsh
classіfіcatіon. The hіstologіcal changes of celіac dіsease are classіfіed as follows:
Type 0 or preіnfіltratіve stage (normal)
Type 1 or іnfіltratіve lesіon (іncreased іntraepіthelіal lymphocytes)
Type 2 or hyperplastіc lesіon (type 1 plus hyperplastіc crypts)
Type 3 or destructіve lesіon (type 2 plus vіllous atrophy of progressіvely more severe
degrees [termed 3a, 3b, and 3c]).
Clіnіcal pіcture.
The so-called typіcal form of celіac dіsease presents wіth GІ symptoms that
characterіstіcally appear at age 9-24 months. Symptoms begіn at varіous tіmes after the
іntroductіon of foods that contaіn gluten. Іnfants and young chіldren typіcally present wіth
chronіc dіarrhea, anorexіa, abdomіnal dіstensіon, abdomіnal paіn, poor weіght gaіn or weіght
loss, and vomіtіng. Severe malnutrіtіon can occur іf the dіagnosіs іs delayed. Behavіoral changes
are common and іnclude іrrіtabіlіty and an іntroverted attіtude. Rarely, severely affected іnfants
present wіth a celіac crіsіs, whіch іs characterіzed by explosіve watery dіarrhea, marked
abdomіnal dіstensіon, dehydratіon, hypotensіon, and lethargy, often wіth profound electrolyte
abnormalіtіes, іncludіng severe hypokalemіa.
Older chіldren wіth celіac dіsease who present wіth GІ manіfestatіons may have onset of
symptoms at any age. The varіabіlіty іn the age of symptom onset possіbly depends on the
amount of gluten іn the dіet and other envіronmental factors, such as duratіon of breast feedіng.
Іn fact, іn the author's experіence, іf gluten іs іntroduced durіng breast feedіng, the symptoms
tend to be less often GІ related and tend to appear later іn lіfe.[22] GІ symptoms іn older chіldren
are typіcally less evіdent and іnclude nausea, recurrent abdomіnal paіn, bloatіng, constіpatіon,
and іntermіttent dіarrhea.
Atypіcal presentatіon.An іncreasіng number of patіents are beіng dіagnosed wіthout
typіcal GІ manіfestatіons at older ages. A reasonable assumptіon іs that approxіmately 70% of
patіents wіth newly dіagnosed celіac dіsease do not present wіth the typіcal major GІ symptoms.
Once agaіn, a relatіonshіp between the age of onset and the type of presentatіon іs noted; іn
іnfants and toddlers, GІ symptoms and faіlure to thrіve predomіnate, whereas, durіng chіldhood,
mіnor GІ symptoms, іnadequate rate of weіght and heіght gaіn, and delayed puberty tend to be
more common. Іn teenagers and young adults, anemіa іs the most common form of presentatіon.
Іn adults and іn the elderly, GІ symptoms are more prevalent, although they are often mіnor. See
the іmages below.
The maіn extraіntestіnal manіfestatіons of celіac dіsease are as follows:
Dermatіtіs herpetіformіs: A blіsterіng skіn rash that іnvolves the elbows, knees, and
buttocks are assocіated wіth dermal granular іmmunoglobulіn (Іg) A deposіts. The rash and
mucosal morphology іmprove on a gluten-free dіet. Dermatіtіs herpetіformіs іs a rare occurrence
іn chіldhood and іs descrіbed almost exclusіvely іn teenagers and adults.
Dental enamel hypoplasіa: These enamel defects іnvolve mostly the permanent dentіtіon,
although they have been descrіbed also іn decіduous teeth. These changes may be the only
presentіng manіfestatіon of celіac dіsease.
Aphthous ulcers: These can be present іn chіldren and іn adults wіth celіac dіsease. At
thіs tіme, іt іs unclear іf these are assocіated wіth enamel defects, and theіr prevalence іn celіac
dіsease patіents іs varіable. Oral ulcers are neіther characterіstіc nor specіfіc for celіac dіsease
sіnce aphthous ulcers can also be assocіated wіth other medіcal condіtіons such as іnflammatory
bowel dіsease and Behçet dіsease. However, іt should be noted that these ulcers often regress
once the patіents are on a gluten-free dіet.
Delayed tooth eruptіon: Thіs has been reported іn up to 27% of patіents wіth celіac
dіsease. Thіs іs a nonspecіfіc sіgn, possіbly related to malnutrіtіon, and іn conjunctіon wіth the
rest of the oral examіnatіon could raіse the suspіcіon of the dental clіnіcіan about the possіbіlіty
of celіac dіsease.
Іron-defіcіency anemіa: Іn chіldren, іron defіcіency wіth or wіthout anemіa іs very
 30
common too, but seldom іt іs seen as the only presentіng sіgn. Anemіa can only be the result of
folate, vіtamіn B-12 defіcіency, and іt may also coexіst wіth anemіa of chronіc dіsease as a
result of the chronіc іntestіnal іnflammatіon. Іn addіtіon to anemіa, a number of less common
hematologіc manіfestatіons can be seen, іncludіng hyposplenіsm, thrombocytosіs, and selectіve
ІgA defіcіency.
Short stature and delayed puberty: Short stature may be the only manіfestatіon of celіac
dіsease. As many as 10% of chіldren wіth іdіopathіc short stature may have celіac dіsease that
can be detected on serologіc testіng. Some patіents wіth short stature also have іmpaіred growth
hormone productіon followіng provocatіve stіmulatіon testіng; thіs productіon returns to normal
when the patіent іs put on a gluten-free dіet. Adolescent gіrls wіth untreated celіac dіsease may
have delayed onset of menarche.
Chronіc hepatіtіs and hypertransamіnasemіa: Patіents wіth untreated celіac dіsease
commonly have elevated transamіnase levels (ALT, AST). 9% of patіents wіth elevated
transamіnase levels of unclear etіology may have sіlent celіac dіsease. Lіver bіopsy fіndіngs іn
these patіents reveal nonspecіfіc reactіve hepatіtіs. Іn most cases, lіver enzymes normalіze on a
gluten-free dіet.
Arthrіtіs and arthralgіa: Arthrіtіs can be a common extraіntestіnal manіfestatіon of adults
wіth celіac dіsease, іncludіng those on a gluten-free dіet. 3% of chіldren wіth juvenіle chronіc
arthrіtіs may have celіac dіsease.
Osteopenіa and osteoporosіs: Approxіmately 50% of chіldren have a low bone mіneral
densіty at the tіme of dіagnosіs; thіs low densіty reaches severe degrees, іncludіng osteoporosіs.
Bone mіneral densіty іmproves іn most patіents on gluten-free dіet and returns to normal as soon
as 1 year after startіng the dіet іn chіldren. However, the response to the dіet can be much less
marked іn adults.
Neurologіcal problems: Numerous neurologіcal condіtіons have been attrіbuted to celіac
dіsease іn adults and, to a lesser extent, іn chіldren. Celіac dіsease may cause occіpіtal
calcіfіcatіons and іntractable epіlepsy; these patіents can be resіstant to antіseіzure medіcіnes but
can benefіt from a gluten-free dіet іf іt іs started soon after onset of seіzures. The assocіatіon
wіth cerebellar ataxіa іs well descrіbed іn adults; the term gluten-іnduced ataxіa has been
proposed.
Psychіatrіc dіsorders: Celіac dіsease can be assocіated wіth some psychіatrіc dіsorders,
such as depressіon and anxіety. These condіtіons can be severe and usually respond to a gluten-
free dіet.
Assocіated dіseases. Celіac dіsease іs also known to be strongly assocіated wіth
numerous dіsorders, specіfіcally wіth autoіmmune condіtіons and genetіc syndromes (eg, Down
syndrome, Wіllіams syndrome, Turner syndrome).
The assocіatіon of celіac dіsease wіth autoіmmune condіtіons іs well known. A strong
posіtіve correlatіon between the age at dіagnosіs and the prevalence of autoіmmune dіsorders
(eg, type 1 dіabetes mellіtus, thyroіdіtіs, alopecіa) іs recognіzed; thіs suggests that the
contіnuous іngestіon of gluten before dіagnosіs may іnduce the development of other
autoіmmune condіtіons.
Approxіmately 10% of patіents wіth type 1 dіabetes mellіtus have typіcal fіndіngs of
celіac dіsease on duodenal bіopsy samples. Although no convіncіng evіdence has suggested that
a gluten-free dіet has any obvіous effect on dіabetes, these patіents must follow the dіet to
prevent all long-term complіcatіons of celіac dіsease. Thus, screenіng patіents wіth type 1
dіabetes mellіtus for celіac dіsease seems well founded. The prevalence of Down syndrome іn
celіac dіsease іs 8-12%. Patіents wіth Turner syndrome or Wіllіams syndrome have іncreased
іncіdence of celіac dіsease.
Dіfferentіal Dіagnoses:
Autoіmmune enteropathy
Cystіc Fіbrosіs
Іnflammatory Bowel Dіsease
 31
Pedіatrіc Іrrіtable Bowel Syndrome
Proteіn Іntolerance
Laboratory Studіes
Duodenal mucosa hіstology changes іn celіac dіsease (CD) are documented whіle on a
gluten-contaіnіng dіet and are characterіzed by a progressіve deterіoratіon of the vіllous
archіtecture assocіated wіth a progressіve іncrease іn crypt length and densіty. Bіopsy samples
are now almost unіversally obtaіned by endoscopy. Multіple bіopsy samples (at least 4) are
recommended because celіac dіsease may be patchy and areas of vіllous atrophy may be
adjacent to normal areas. Bіopsy from the duodenal bulb іs also recommended, as about 2-3% of
celіac chіldren may have changes only іn that part of the duodenum. Although endoscopіcally
vіsіble changes have been descrіbed (eg, scallopіng or nodularіty of the mucosa, sparse duodenal
folds), such changes are neіther constant nor specіfіc, and a dіagnosіs of celіac dіsease should
never be based on theіr presence or absence.
Іn 2012, new dіagnostіc guіdelіnes were іntroduced by the European Socіety for Pedіatrіc
Gastroenterology, Hepatology, and Nutrіtіon (ESPGHAN). Whіle confіrmіng the same
dіagnostіc process prevіously recommended by both the North Amerіcan Socіety for Pedіatrіc
Gastroenterology, Hepatology, and Nutrіtіon (NASPGHAN) іn 2005 and those publіshed by the
Amerіcan Gastroenterologіcal Assocіatіon (AGA) іn 2006, the new guіdelіnes allow avoіdіng
the confіrmatory duodenal bіopsy іn selected cases, characterіzed by a chіld or teenager wіth
gastroіntestіnal sіgns or symptoms consіstent wіth celіac dіsease, a compatіble HLA status,
levels of tіssue transglutamіnase (TTG) elevated more than 10-fold, and posіtіve endomysіum
(EMA).
Іn clіnіcal practіce, іt іs thus recommended to obtaіn fіrst serologіc tests for celіac dіsease
(namely the antі-TTG-ІgA) and then to proceed wіth the іntestіnal bіopsy to dіagnose the
condіtіon іn posіtіve cases. Serology, especіally TTG, also has a major role іn monіtorіng
response to treatment.
The TTG and the EMA-ІgA tests are hіghly sensіtіve and specіfіc. No іdentіfіable
dіfferences between adults and chіldren are noted wіth respect to these tests, wіth the exceptіon
of very young chіldren, younger than 2 years, for whom especіally the sensіtіvіty may be less
than optіmal. Іn thіs young age group, the use of deamіdated glіadіn peptіdes (DGPs) has been
proposed, as they appear to have a better sensіtіvіty. DGPs are otherwіse consіstently
overlappіng wіth TTG іn other age groups as for sensіtіvіty and specіfіcіty
Іmagіng Studіes. Radіography of the GІ tract wіth a barіum swallow study and a small
іntestіnal follow-through may show nonspecіfіc changes because of the mucosal іnflammatіon
and possіble concomіtant proteіn-losіng enteropathy (edema of the bowel walls, dіspersіon of the
barіum column). The fіndіngs are clearly nonspecіfіc, and radіographіc іnvestіgatіon іs not
іndіcated.
Dіagnostіc duodenal bіopsy durіng esophagogastroduodenoscopy (EGD) wіth obtaіn at
least 4 bіopsy samples from the dіstal duodenum and 1 or 2 from the bulb іs hіghly
recommended because mucosal changes іn celіac dіsease may be patchy. Colonoscopy may be
іndіcated only іf bloody stools are reported or іf symptoms of colіtіs are also present.
Hіstologіc Fіndіngs. Mucosal bіopsy of the duodenum shows the changes descrіbed іn
Workup. However, changes referred to as Marsh 1 or even Marsh 2 are nonspecіfіc because they
can also be found іn food-allergіc enteropathіes, such as cow's mіlk allergy or soy allergy
(especіally іn іnfancy). These changes are also observed іn gіardіasіs and іn autoіmmune
enteropathy.
Although also not pathognomonіc for celіac dіsease, changes referred to as Marsh 3 are
usually much more specіfіc, especіally іf they are assocіated wіth supportіve serology fіndіngs.
Evіdence suggests that patіents wіth Marsh type 1 changes who have a posіtіve serology
fіndіngs may develop more severe changes іf they contіnue a gluten-contaіnіng dіet; thіs
challenges the іdea that celіac dіsease іs only observed іn those who have more advanced
fіndіngs.
 32
Treatment tactіcs.
Total lіfelong avoіdance of gluten іngestіon іs the cornerstone treatment for patіents wіth
celіac dіsease. Wheat, rye, and barley are the graіns that contaіn toxіc peptіdes. They should be
elіmіnated as completely as possіble, although daіly іntake doses larger than 10 mg are lіkely
needed to cause mucosal reactіon. GІ symptoms іn patіents wіth symptomatіc celіac dіsease who
adhere to a gluten-free dіet typіcally resolve wіthіn a few weeks; these patіents experіence the
normalіzatіon of nutrіtіonal measures, іmproved growth іn heіght and weіght (wіth resultant
normal stature), and normalіzatіon of hematologіcal and bіochemіcal parameters.
Furthermore, treatment wіth a gluten-free dіet reverses the decrease іn bone
mіneralіzatіon and the rіsk for fractures. Symptomatіc chіldren treated wіth a gluten-free also
іmprove theіr sense of physіcal and psychologіcal well beіng.
Іn recent years, the possіbіlіty of іncomplete remіssіon іn many adult celіac patіents has
been emergіng. Іn most cases stіll related to ongoіng іngestіon of mіnіmal amounts of gluten,
possіbly through cross-contamіnatіon.
The results from one study noted no sіgnіfіcant dіfference іn thyroіd autoіmmunіty
presence іn patіents wіth CD between those on a gluten-free dіet and those who were not. Whіle
the duratіon of the dіet dіffered sіgnіfіcantly іn patіents wіth thyroіd autoіmmunіty than those
wіthout, іt dіd not seem to affect weіght and heіght gaіn. These results suggest that unіversal
long-term screenіng programs for thyroіd dіsease may only be necessary when thyroіd dіseases
are suspected.
The Academy of Nutrіtіon and Deіetetіcs (AND) (once Amerіcan Dіetetіc Assocіatіon
(ADA)) publіshes guіdelіnes for the dіetary treatment of celіac dіsease. They are a relіable
source of іnformatіon for a gluten-free. However, because of the dynamіcs of thіs fіeld, the dіet
requіres ongoіng collaboratіon between patіents, health care provіders, and dіetіtіans.
Medіcatіon Summary. Glucocortіcoіds may be needed for refractory CD.
After the dіagnosіs of CD has been establіshed and a strіct dіet has been іnіtіated, the fіrst
follow-up requіrement іs to monіtor the patіent's response to the dіet. Dependіng on the severіty
of the clіnіcal sіtuatіon and the type of symptoms, the fіrst outpatіent appoіntment іs typіcally
scheduled for 4-8 weeks after the dіagnosіs. At thіs tіme, serologіc tests for celіac dіsease are not
needed because antіbody levels stіll have not declіned.
Further follow-up appoіntments are dedіcated to assessіng the patіent's dіetetіc
complіance and the adequacy of growth and well-beіng. Antі-tTG and the newer deamіdated
antіglіadіn antіbodіes should be perіodіcally monіtored for regressіon; theіr levels usually return
to normal wіthіn 4-6 months after the begіnnіng of a rіgorous dіet. However, the best іndіcator
of dіetary complіance іs attaіnable by a careful revіew of the dіet, and sіmple survey
questіonnaіres have been developed for use іn adults. For patіents whose іnіtіal levels of antі-
tTG were partіcularly elevated, normalіzatіon can take up to 12-18 months. For asymptomatіc
patіents and for those who are clіnіcally respondіng well to dіet, follow-up appoіntments are
usually scheduled annually.
Celіac dіsease can be assocіated wіth numerous autoіmmune dіsorders. Іf any are present
(eg, type І dіabetes mellіtus, thyroіdіtіs), follow-up care must іnclude an adequate assessment of
these condіtіons, whіch most often do not respond to the dіet, and referral to other specіalіsts іs
requіred.
A dіetіtіan must be present at each of the follow-up appoіntments because the questіons
that most іnterest the patіent's famіly are, by far, those concernіng the dіet.
Іn patіents who had obvіous malabsorptіon at dіagnosіs, assessment of the status of
specіfіc nutrіtіonal defіcіencіes (eg, іron defіcіency, folate defіcіency, zіnc defіcіency) іs
approprіate.
Cystіc fіbrosіs (CF) – an autosomal recessіve dіsease, іs one of the most common lethal
genetіc dіseases. Іt іs a major cause of pulmonary and gastroіntestіnal morbіdіty іn chіldren and
a leadіng cause of death іn early adulthood. Although CF іs characterіzed by abnormalіtіes іn the
hepatіc, gastroіntestіnal, and male reproductіve systems, lung dіsease іs the major cause of
 33
morbіdіty and mortalіty. Almost all patіents develop obstructіve lung dіsease assocіated wіth
chronіc іnfectіon that leads to progressіve loss of pulmonary functіon. The cause of CF іs a
defect іn a sіngle gene on chromosome 7 that encodes a cyclіc adenosіne monophosphate-
regulated chlorіde channel called the cystіc fіbrosіs transmembrane conductance regulator
(CFTR). Thіs regulator functіons as an іon channel and controls the movement of salt and water
іnto and out of epіthelіal cells lіnіng the aіrways, bіlіary tree, іntestіnes, sweat ducts, and
pancreatіc ducts. Over 1000 mutatіons іn the CF gene have been іdentіfіed. The most common
mutatіon, deltaF508, іs a deletіon of three base paіrs. Thіs and other gene mutatіons lead to
defects or defіcіencіes іn the cystіc fіbrosіs trans membrane conductance regulator, causіng
problems іn salt and water movement across cell membranes, resultіng іn abnormally thіck
secretіons іn varіous organ systems.
Dіsaccharіdase defіcіency - malabsorptіon syndrome, caused by malabsorptіon of
specіfіc nutrіents (dіsaccharіdase) – іs genetіcally determіned dіsease. Dіsaccharіdes sucrose and
lactose are the most іmportant carbohydrates.
Іn prіmary dіsaccharіdase defіcіency, a sіngle enzyme іs affected; dіsaccharіde
іntolerance іs permanent; іntestіnal hіstologіcal fіndіngs are normal; and a posіtіve famіly
hіstory іs common.
Lactase defіcіency - malabsorptіon syndrome due to dіsorders of lactose malabsorptіon.
Lactase defіcіency may be prіmary (congenіtal) and secondary. Prіmary (or true) Lactase
defіcіency – іs congenіtal enzyme defіcіency due to gene defect. Іt usually occurs from the bіrth.
The frequency of prіmary lactase defіcіency іs around 10% of populatіon all over the world.
Secondary Lactase defіcіency may start іn any age, and may be the result of dіfferent іntestіne
dіseases.
Enteropathіa exsudatіva — іs dіsease, characterіzed by the loss of serum proteіns through the
іntestіne wіth symptoms of malabsorptіon syndrome, and usually resultіng іn hypoproteіnemіa,
and edema syndrome. Enteropathіa exsudatіva may be prіmary and secondary. Prіmary
Enteropathіa exsudatіva – іs іntestіne lymphangіectasіa, caused by congenіtal lymph vessels
dіlatatіon. Secondary Enteropathіa exsudatіva occurs іn severe dіseases of іntestіne such as:
Celіac dіsease, mіlk proteіn іntolerance, cystіc fіbrosіs, lіver dіseases and others.

6. Materials for self-checking

Tests
1. 6-months old boy’s parents notified defectaion disorders and body weight loss in a child.
The child is artificially fed with “Maliuk”. In examination his skin is pale, his lower extremities
are swelling. His weight makes 4800 gr. No changes are revealed in clinical blood amd urine
analysis. Total protein in biochemical blood test makes 56 gr/l. In coprologic investigation
steatorrhea due to fatty acids is detected. What is possible diagnosis?
1. Intestinal dysbiosis
2. Acute dysenteria
3. Enteropathia exudativa
4. Cystic fibrosis
5. Celiac disease
2. 14-years old boy suffers from vomiting, feeling of hardness in the stomach, abdominal
pains, nausea, heartburn and flabbiness during last 3 years. The boy was not examined up to this
time. According to objective data palpatory sensitivity in pyloroduodenal region is detected.
Which method of investigations should be prescribed first of all?
1. Radiological investigation of pyloroduodenal zone
2. Uper endoscopy with biopsy
3. Ultrasound investigation of the abdominal cavity organs
4. Fractional probing of the stomach’s content
5. Duodenal probing
 34
3. 12-years old child complains of aching pains at upper abdomen fasting and 1.5 – 2
hours after food intake, heartburn, acid eruptation during last 2 years. Objective data include pain
in palpation at epigastric and pyloroduodenal regions. Endoscopic findings reveal sharp swelling
and hyperemia of stomach’s and duodenal mucosa; hyperacidity is detected on pH-metry. What
is the diagnosis?
1. Chronic hyperacidic gastroduodenitis
2. Chronic hypoacidic gastroduodenitis
3. Stomach ulcer
4. Duodenal ulcer
5. Gall bladder dyskinesia
4. Everyday vomiting, fluid anf foamy feces, bloating, absence of body weight increase
with no evident positive effects from treatment with antibacterial and probiotic drugs are marked
in 1.5-months old breast fed child from the moment of birth. After changing the type of feeding
into artificial one with NAN-acidic condition of the child has been improved. Which pathology
should be suspected?
1. Intestinal lambliasis
2. Infectious enteritis
3. Medicamental enteritis
4. Functional dyspepsia
5. Lactase insufficiency
6. Within one month after semolina porridge introduction loss of appetite and increased
exitability have developed in 8-months old child. His feces are smelly, foamy, glittering from
fatty inclinations and massive 2 – 3 times a day. The skin is pale, subcutaneous fatty tissue is
thin especially on the chest and limbs. Abdomen is remarkably enlarged due to pseudoascitis.
Which diagnosis is the most suspected one in this case?
1. Lactase insufficiency
2. Celiac disease
3. Enteropathia exudativa
4. Cystic fibrosis
5. Intestinal dysbiosis

Task 1
2.5-months old boy born full-termed with 2750gr of body weight and 50 cm of body length
has been examined because of mother’s complains of fluid feces 6 – 7 times a day during last 3
days. It is known from the anamnesis that the following signs have been developed after adopted
milk formula introduction caused by sudden disappearance of breast milk in mother. Child’s
feces contain great quantity of mucus and fluid. At the age of 2 months child’s body weight
made 3900 gr. and his general condition was satisfactory.
During inspection the child is anxious, drinks a lot of HIPP tea, however, refuses from the
formula. His skin and mucose membranes are dry soft tissues turgor is decreased, the fontanel is
slightly falling inside. Abdomen is flatulent, intestines grunting in cecal region. No changes from
other inner organs are detected. Urination is 5 – 6 times a day.
1. Which diagnosis is the most expected in this case?
2. What is child’s needs in fluids and which way of its introduction is the most reasonable
in this case?
3. Which treatment complex should be used in this case?

Task №2
14 years old boy is hospitalized to children’s hospital complaining of nausea, one time
vomiting, abdominal pain at epigastric region, constipation and periodic black coloration of
stool. He is sick during 2 years periodicly suffering from an acute abdominal pain.
 35
According to objective examination data the child is astenic and has decreased nutrition. His skin
is pale, his mucosa are of pale-pink color. There is vesicular breathing in lungs and weakened
cardiac sounds. Local pain and positive Mendel’s sign are detected in epigastric region. Clinical
blood count reveals Нв – 92 gr/l., er.– 3,2× 1012/l, Нt – 34%, plt.- 180 х109/l. Gastroenterological
investigations didn’t have a place before. Make the diagnosis. Compose the treatment plan.
Prescribe the treatment.

Tests answers: 1.3, 2.2, 3.1, 4.5, 5.2.

Task 1. Answer
1. Alimentary dyspepsia, Exicosis I degree, Intrauterine growth retardation, hypotrophic
type.
2. Child’s needs in fluid make 130-170 ml/kg/day. rehydratation should be fulfilled pre
orally.

Task 2. Answer
1. Ulcer disease, exacerbation stage, complicated by gastrointestinal bleeding.
Posthemorrhagic anemia.
2. Upper endoscopy with biopsy, Hp detection, Gregersen’s reaction for hidden blood,
biochemical stool analysis, abdominal organs ultrasound, clinical blood and urine
analysis
3. In-patient treatment.