THE MINISTRY OF HEALTH OF UKRAINE

BOGOMOLETS NATIONAL MEDICAL UNINERSITY

“Approved”
on Pediatric department № 1
methodic meeting
The head of the department
Berezenko V.S.
“______” _____________ 2021

METHODIC GUIDELINES

FOR PREPARATION OF STUDENTS

FOR A PRACTICAL CLASS

Studying discipline Pediatry

Module № 1

Thematic module № 1

Topic of the class №1 The most widespread functional and organic intestinal diseases
in children (irritable bowel syndrome, lactase insufficiency,
celiac disease, Unspecific ulcerative colitis, Crohn’s disease)

Course 4

Faculty Medical

Kyiv 2021
1. Actuality of the topic. Intestinal diseases occupy over 10% in the digestive pathology structure.
Intestinal diseases structure includes both functional and inflammatory processes causing variability
of their clinical manifestations in children. A special place is occupied by hereditary intestinal
diseases accompanying with malabsorption syndrome. It is necessary to remember about individual
peculiarities of the large intestine motor function, variants of norm connected with each period of
childhood. The problem of correction and treatment of hereditary primary disorders of
carbohydrates, proteins, fats, vitamins and electrolytes absorption is still very actual nowadays.

2. Concrete aims

 To know age anatomic and physiologic peculiarities of the digestive system building
 To analyze reasons and mechanisms of development of functional and organic intestinal
diseases in children
 To study diagnosing the most widespread intestinal diseases in children
 To know classification of functional and organic intestinal diseases in children
 To be able to evaluate the results of laboratory and functional investigations of the most
widespread intestinal diseases in children
 To be able to compose the plan of treatment and rehabilitation in the most widespread
intestinal diseases in children

3. Theoretical answers for the class

1. Intestinal diseases classification
2. Clinical and laboratory criteria of IBS diagnostics
3. IBS treatment principles
4. Pathogenetic theories of IBS development in children
5. Main indications for IBS hormonal therapy
6. Laboratory and instrumental investigations used for Crohn’s disease diagnostics
7. Lactase insufficiency classification
8. Main directions of lactase insufficiency treatment
9. Laboratory and instrumental diagnostics of celiac disease
10. Celiac disease treatment principles

4. Practical tasks fulfilled during the class

1. Participation in demonstration of the patient
2. Independent curation of the patient
3. Investigation plan composition
4. Differential diagnostics, evaluation of laboratory and instrumental investigations results
5. Composition of a treatment plan
6. Making up of the practical work results

5. Contents of the topic

H2b. Irritable Bowel Syndrome (IBS)
Epidemiology. In Western countries, IBS was diagnosed in 6% of middle school and 14% of
high school students by using Rome I criteria. According to Rome II criteria, IBS was diagnosed in
0.2% of children (mean age, 52 months) seen by primary care pediatricians and in 22%– 45% of
children aged 4 –18 years presenting to tertiary care clinics.

Diagnostic criteria* for Irritable Bowel Syndrome

 Must include all of the following:
1. Abdominal discomfort (an uncomfortable sensation not described as pain) or pain
associated with 2 or more of the following at least 25% of the time:
a. Improved with defecation
b. Onset associated with a change in frequency of stool
c. Onset associated with a change in form (appearance) of stool
2. No evidence of an inflammatory, anatomic, metabolic, or neoplastic process that explains
the subject’s symptoms
*Criteria fulfilled at least once per week for at least 2 months before diagnosis.

Symptoms that cumulatively support the diagnosis of IBS are (1) abnormal stool frequency (4
or more stools per day and 2 or less stools per week), (2) abnormal stool form (lumpy/hard or
loose/watery stool), (3) abnormal stool passage (straining, urgency, or feeling of incomplete
evacuation), (4) passage of mucus, and (5) bloating or feeling of abdominal distention.
Physiological features. Visceral hypersensitivity has been documented in children with IBS. It
may be related to numerous processes, including infection, inflammation, intestinal trauma, or
allergy, and may be associated with disordered gut motility. Genetic predisposition, early stressful
events, and ineffective patientcoping mechanisms are compounding factors.
Psychological features. Anxiety, depression, and multiple other somatic complaints have been
reported by IBS children and their parents. Social learning of illness behavior may contribute to the
development of IBS.
Clinical evaluation. Symptoms of abdominal pain that meet Rome criteria for IBS in the
presence of a normal physical examination and growth curve with the absence of alarm signals
substantiate a positive diagnosis. Potential triggering events and psychosocial factors are important
to explore. Education about mechanisms leading to IBS avoids unnecessary invasive testing.
Treatment. A confident diagnosis, confirmation, and explanation of pain experience and
reassurance can by itself be therapeutic. Specific goals of therapy include modifying severity and
developing strategies for dealing with symptoms. Controlled data on therapeutic interventions are
limited to peppermint oil that may provide some benefit in children with IBS but not in adults.
Inversely, the efficacy of some antidepressants and serotonic agents is well shown in adults with
IBS, but there are only anecdotal reports concerning their use in children with chronic abdominal
pain.

Nonspecific ulcerative colitis

Ulcerative colitis is one of the 2 major types of inflammatory bowel disease (IBD), along
with Crohn disease. Unlike Crohn disease, which can affect any part of the gastrointestinal tract,
ulcerative colitis characteristically involves the large bowel.
The exact etiology of ulcerative colitis is unknown, but the disease appears to be
multifactorial and polygenic. Proposed causes include environmental factors, immune dysfunction,
and a likely genetic predisposition. Some have suggested that children of below-average birth
weight who are born to mothers with ulcerative colitis have a greater risk of developing the disease.
Histocompatibility human leukocyte antigen (HLA)–B27 is identified in most patients with
ulcerative colitis, although this finding is not causally associated with the condition and the finding
of HLA-B27 does not imply a substantially increased risk for ulcerative colitis. Ulcerative colitis
might also be influenced by diet, although diet is thought to play a secondary role. Food or bacterial
antigens might exert an effect on the already damaged mucosal lining, which has increased
permeability.
 Ulcerative colitis is a lifelong illness that has a profound emotional and social impact on
affected patients.
Grossly, the colonic mucosa appears hyperemic, with loss of the normal vascular pattern. The
mucosa is granular and friable. Frequently, broad-based ulcerations cause islands of normal mucosa
to appear polypoid, leading to the term pseudopolyp.
The bowel wall is thin or of normal thickness, but edema, the accumulation of fat, and
hypertrophy of the muscle layer may give the impression of a thickened bowel wall. The disease is
largely confined to the mucosa and, to a lesser extent, the submucosa. Muscle-layer and serosal
involvement is very rare; such involvement is seen in patients with severe disease, particularly toxic
dilatation, and reflects a secondary effect of the severe disease rather than primary ulcerative colitis
pathogenesis. Early disease manifests as hemorrhagic inflammation with loss of the normal vascular
pattern; petechial hemorrhages; and bleeding. Edema is present, and large areas become denuded of
mucosa. Undermining of the mucosa leads to the formation of crypt abscesses, which are the
hallmark of the disease.
Patients with ulcerative colitis predominantly complain of rectal bleeding, with frequent
stools and mucous discharge from the rectum. Some patients also describe tenesmus. Onset is
typically insidious. In severe cases, purulent rectal discharge causes lower abdominal pain and
severe dehydration, especially in the elderly population.
Ulcerative colitis manifests as an intense inflammatory reaction in the large intestine. Rarely,
patients have persistence of small intestinal inflammation following proctocolectomy and pull-
through.
Fulminant disease
In some cases, ulcerative colitis has a fulminant course marked by severe diarrhea and
cramps, fever, leukocytosis, and abdominal distention. Fulminant disease occurs more often in
children than in adults. An estimated 15% of patients present with an attack severe enough to
require hospitalization and steroid therapy. Children may also present with systemic complains,
including fatigue, arthritis, failure to gain weight, and delayed puberty. The differential diagnosis of
these symptoms in the pediatric population includes many entities, and definitive diagnosis may be
delayed.
Extracolonic manifestations
Ulcerative colitis is associated with various extracolonic manifestations. These include
uveitis, pyoderma gangrenosum, pleuritis, erythema nodosum, ankylosing spondylitis, and
spondyloarthropathies. Uveitis is the most common, with an incidence of 3.8%, followed by
primary sclerosing cholangitis at 3%, ankylosing spondylitis at 2.7%, erythema nodosum at 1.9%,
and pyoderma gangrenosum at 1.2%. However, reports vary, and some have stated that the
incidence of ankylosing spondylitis is as high as 10%. Arthropathies occur in as many as 39% of
patients with inflammatory bowel disease. About 30% of such patients have inflammatory back
pain, 10% have synovitis, and as many as 40% have radiologic findings of sacroiliitis.
Findings from abdominal examination are usually unremarkable. Physical findings are
typically normal in patients with mild disease, except for mild tenderness in the lower left
abdominal quadrant.
Patients with severe disease can have signs of volume depletion and toxicity, including the
following:
 Fever
 Tachycardia
 Significant abdominal tenderness
 Weight loss
 The severity of ulcerative colitis can be graded as follows:
 Mild - Bleeding per rectum and fewer than 4 bowel motions per day
 Moderate - Bleeding per rectum with more than 4 bowel motions per day
 Severe - Bleeding per rectum, more than 4 bowel motions per day, and a systemic illness with
hypoalbuminemia (< 30 g/L)

 Distinguishing Ulcerative colitis from Crohn Disease

Ulcerative Colitis Crohn Disease
Only colon involved Panintestinal
Continuous inflammation extending proximally from Skip-lesions with intervening normal
rectum mucosa
Inflammation in mucosa and submucosa only Transmural inflammation
No granulomas Noncaseating granulomas
Perinuclear ANCA (pANCA) positive ASCA positive
Bleeding (common) Bleeding (uncommon)
Fistulae (rare) Fistulae (common)

The diagnosis of ulcerative colitis is best made with endoscopy and mucosal biopsy for
histopathology. Laboratory studies are helpful to exclude other diagnoses and assess the patient's
nutritional status, but serologic markers can assist in the diagnosis of inflammatory bowel disease.
Radiographic imaging has an important role in the workup of patients with suspected inflammatory
bowel disease and in the differentiation of ulcerative colitis from Crohn disease by demonstrating
fistulae or the presence of substantial coexisting more proximal small bowel disease in a patient
who turns out to actually have Crohn disease.
The initial treatment for ulcerative colitis includes corticosteroids, anti-inflammatory agents,
antidiarrheal agents, and rehydration. Surgery is considered if medical treatment fails or if a surgical
emergency develops.

Crohn disease
Crohn disease is a chronic inflammatory bowel disease. Once considered rare in the pediatric
population, it is recognized with increasing frequency among children of all ages. Approximately
20-30% of all patients with Crohn disease present when they are younger than 20 years.
The etiology of Crohn disease is multifactorial. An interaction between the predisposing
genetic factors, environmental factors, host factors, and triggering event is necessary for the disease
to develop.
The pathogenesis of Crohn disease is multifactorial. After a triggering event occurs in a
genetically susceptible individual, an altered immune response leads to chronic inflammation of the
intestine. Although the etiology of the precipitating event is unknown, luminal bacteria or specific
antigens are thought to be involved.
Chronic inflammation from T-cell activation leading to tissue injury is implicated. After
activation by antigen presentation, unrestrained responses of helper lymphocytes type 1 (Th1)
predominate because of defective regulation. Th1 cytokines (eg, interleukin [IL]–12 and tumor
necrosis factor [TNF]-α) stimulate the inflammatory response. Inflammatory cells recruited by these
cytokines release nonspecific inflammatory substances (eg, arachidonic acid metabolites, proteases,
platelet activating factor, and free radicals), which directly injure the intestine.
The macroscopic findings at the time of endoscopy or colonoscopy or surgery include various
degrees of edema, erythema, ulceration, friability, thickening of the bowel wall and mesentery, and
extension of fat over the serosal surface of the intestine.
Skipped areas of inflammation anywhere in the upper or lower GI tract are characteristic of
Crohn disease, in contrast to the continuous diffuse colonic inflammation found with ulcerative
colitis. Microscopic findings on intestinal mucosal biopsy consist of chronic inflammation with
architectural distortion. Granulomas are sometimes noted on biopsy findings in Crohn disease but
never in UC; their presence can be useful in distinguishing between these 2 entities.
Children with Crohn disease of the small intestine usually present with evidence of
malabsorption, including diarrhea, abdominal pain, growth deceleration, weight loss, and anorexia.
Initially, these symptoms may be quite subtle. The onset of growth failure is usually insidious, and
any child or adolescent with persistent alterations in growth should undergo appropriate diagnostic
evaluation for Crohn disease. Growth failure may precede GI symptoms by years.
Findings on physical examination depend on the duration and extent of the disease and on the
extraintestinal manifestations.
Careful assessment of growth and development is an important part of evaluating the pediatric
patient. Growth abnormalities may be detected by evaluating height and weight, percentage height
and weight for the patient’s age and percentage weight for the patient’s height, growth velocity,
body composition on anthropometry, and skeletal bone age. The most sensitive indicator of growth
abnormalities is a decrease in growth velocity, which may be observed before the major percentile
lines on standard growth curves are crossed.
Vital signs are usually normal, although tachycardia may be present with anemic patients.
Chronic intermittent fever is a common presenting sign. Body weight and height may reveal weight
loss and growth delay.
Abdominal findings may vary from normal to those of an acute abdomen. Diffuse abdominal
tenderness is often present. Fullness or a discrete mass may be appreciated, typically in the right
lower quadrant of the abdomen, which may represent a palpable thickened loop of bowel. Perianal
disease (eg, skin tags, abscesses, fistulae, fissures) is present in approximately 45% of patients.
Pubertal delay may precede the onset of intestinal symptoms, and accurate Tanner staging should be
a part of routine physical examination.
The most common cutaneous manifestations of Crohn disease are erythema nodosum and
pyoderma gangrenosum. Skin examination may also reveal pallor in patients with anemia or
jaundice in those with concomitant liver disease. Eye examination may reveal episcleritis. For the
diagnosis of uveitis, a slit lamp examination by an experienced physician is necessary.
The most common extraintestinal manifestations of Crohn disease are arthritis and arthralgia.
The large joints (eg, hips, knees, ankles) are typically involved.
Laboratory data for Crohn disease are nonspecific. The complete blood count (CBC) may
reveal evidence of hypochromic microcytic anemia due to the iron deficiency anemia secondary to
gastrointestinal blood loss, or it may reveal normocytic anemia due to the anemia of chronic
disease.
levels of acute-phase reactants, the erythrocyte sedimentation rate (ESR), and C-reactive
protein (CRP) levels are often elevated in patients with Crohn disease. However, a normal ESR or
CRP level should not deter further evaluation in a suspicious case.
 Hypoalbuminemia is a common laboratory finding in patients with Crohn disease. Additional
common deficiencies include iron and micronutrients (eg, folic acid, vitamin B-12, serum iron, total
iron binding capacity, calcium, and magnesium).
Stool studies should be obtained to rule out bacterial or parasitic infection.
Serologic testing for inflammatory bowel disease (IBD) is available. Immunoglobulin A (IgA)
and immunoglobulin G (IgG) antibodies to anti– Saccharomyces cerevisiae(ASCA) have been
associated with Crohn disease, whereas perinuclear antineutrophil cytoplasmic antibody (p-ANCA)
has been associated with ulcerative colitis (UC).
Although these tests might assist in differentiating between Crohn disease and UC, they are
not good screening tests. In a retrospective review, serologic screening that included ASCA,
pANCA, and antibody to Escherichia coli outer membrane porin (anti-OmpC) demonstrated a
sensitivity of 60%, a specificity of 91%, and a positive predictive value of 60%.
Excretion of fecal calprotectin, a protein derived from neutrophils, is increased with colorectal
inflammation. Enzyme-linked immunosorbent assay (ELISA) for fecal calprotectin is available; the
cutoff level is 50 µg/g feces.
A single-contrast upper GI radiologic series with small-bowel follow-through (SBFT) can be
used to evaluate the small intestine, which cannot be reached during endoscopy (see the image
below).
Magnetic resonance enterography (MRE) and computed tomography enterography (CTE) are
increasingly being used for evaluation of the small bowel. Both modalities are as sensitive and
specific as SBFT for detection of small bowel inflammation and may be more accurate for detection
of extraenteric complications, including fistulae and abscesses. MRE is a particularly attractive
option because of the lack of radiation exposure.
Proximal small bowel Crohn disease is present in up to 35% of children with this chronic
inflammatory bowel disorder. It is also regarded as a more severe clinical phenotype that is
associated with significant morbidity, including poor growth. MRE has now become the
radiological procedure of choice in identifying proximal small bowel disease in children with Crohn
disease. Moreover, the increased sensitivity of MRE to detect early-onset disease may allow
physicians to tailor therapy more effectively.
Abdominal ultrasonography (US) can be used to investigate intestinal disease and to rule out
gallbladder and kidney stones. Positron emission tomography (PET) is an experimental diagnostic
tool.
The development of flexible, small-caliber endoscopes has allowed colonoscopic evaluation
of pediatric patients of all ages, including infants. Colonoscopy with several colonic and terminal
ileal biopsies is invaluable and considered a standard in the diagnosis of Crohn disease
Upper endoscopy, or esophagogastroduodenoscopy (EGD), should be part of the first-line
investigation in all new cases of suspected Crohn disease. It is useful in planning therapy and in
differentiating between Crohn disease and UC, especially if granulomas are present. Clinically
significant upper GI inflammation can be present in the absence of upper GI symptoms.
Video capsule endoscopy is increasingly being used to evaluate for small-bowel Crohn
disease in children. Before the procedure is initiated, a dissolvable patency capsule should be placed
or small bowel imaging performed to ensure that there are no areas of narrowing or stricture where
the video capsule might create an obstruction.
The microscopic findings in intestinal biopsy samples from pediatric patients with Crohn
disease consist of edema, inflammation (mononuclear and polymorphonuclear), cryptitis and crypt
abscesses, architectural crypt changes, and transmural extension of the inflammation
 The presence of granulomas may be helpful in differentiating between UC and Crohn disease,
but granulomas are present in only about 30% of biopsy specimens obtained from patients with
Crohn disease.

Treatment
5-Acetylsalicylic acid. Although oral 5-ASA preparations are commonly used, adult meta-
analyses suggest that these preparations do not have a clinically important treatment effect on active
Crohn disease and are not superior to placebo for the maintenance of remission in Crohn
disease. Topical 5-ASA therapy is available in suppository and enema forms for the treatment of
distal colitis.
Antibiotics. A few small studies have shown the usefulness of antibiotic therapy in the
treatment of Crohn disease. Metronidazole, as well as the combination of metronidazole and
ciprofloxacin, is useful in the management of perianal disease and of small bowel and colonic
disease.
Nutritional therapy. Nutritional therapy is another important modality for the treatment of
disease, malnutrition, and growth failure in Crohn disease. A dramatic reversal of malnutrition and
a change in growth velocity can be expected in all children treated with adequate nutrition in
conjunction with medical therapy to control symptoms of Crohn disease. Additionally, exclusive
enteral nutrition has been shown to be as effective as corticosteroids for the induction of remission
and might promote better GI tract mucosal healing.
Because most patients have appetite suppression, overnight nasogastric feedings are often
used. Although the exact mechanism of action is unknown, the beneficial effects of this approach
could be due to alteration of the intestinal flora, a decrease in the antigen load, and reductions in
inflammatory cytokine levels.
Corticosteroids. Corticosteroids are the mainstay of therapy for acute exacerbations because
they suppress acute inflammation, thereby providing rapid symptomatic relief. Systemic
corticosteroids are not indicated for maintenance therapy. Enteric coated ileal-release preparations
have been developed for the treatment of ileal and cecal Crohn disease; systemic effects are
decreased with these formulations.
Immunomodulators. Immunomodulators have been used to induce and maintain long-term
remission in chronically active, steroid-dependent or steroid-refractory, moderate-to-severe
pediatric Crohn disease.
6-Mercaptopurine (6-MP) and its prodrug, azathioprine, are effective for the induction and
maintenance of remission and the reduction of corticosteroid exposure in pediatric Crohn disease.
Three months is often required to achieve therapeutic efficacy, although the onset of action varies.
Thiopurine methyltransferase (TPMT) activity should be measured before the initiation of
therapy to identify patients predisposed to altered drug metabolism (which increases the risk of
leukopenia). Measurement of 6-thioguanine nucleotide (6-TG) metabolites is helpful in assessing
compliance and adjusting therapy.
MTX is effective in inducing and maintaining remission in chronic Crohn disease in adults
and has been shown to be effective and well tolerated for maintenance of remission in children. [15,
16, 17, 18]
MTX has a quicker onset of action than 6-MP does, and the once-weekly dosing is
sometimes preferred. Whether oral therapy is as effective as parenteral administration is unclear.
Surgery is considered when medical therapy fails.[23] Indications include intractable disease
with growth failure, obstruction or severe stenosis, abscess requiring drainage, perianal fistulae,
intractable hemorrhage, and perforation.
 Recurrence of disease at the anastomotic site is common after resection. Surgical treatment
for Crohn disease, unlike that for ulcerative colitis (UC), is not curative. Laparoscopic techniques
are becoming the standard of care for most inflammatory bowel disease (IBD) procedures, resulting
in decreased recovery time.
Although Crohn disease may have a sizable effect on the life of a child or adolescent, with
appropriate treatment and support, the prognosis is good, and the risk of a fatal outcome is
extremely low.
Death from Crohn disease is extremely rare in children and adolescents. Severe and
complicated Crohn disease may result in prolonged hospitalizations, multiple surgical procedures,
growth failure, malnutrition, pubertal delay, and poor quality of life.

Lactose intolerance
Lactose intolerance is a common disorder and is due to the inability to digest lactose into its
constituents, glucose and galactose, secondary to low levels of lactase enzyme in the brush border
of the duodenum.
Lactose, a disaccharide, is present in milk and processed foods. Dietary lactose must be
hydrolyzed to a monosaccharide in order to be absorbed by the small intestinal mucosa. A
deficiency of intestinal lactase prevents hydrolysis of ingested lactose. The osmotic load of the
unabsorbed lactose causes secretion of fluid and electrolytes until osmotic equilibrium is reached.
Dilation of the intestine caused by the osmosis induces an acceleration of small intestinal transit,
which increases the degree of maldigestion. Within the large intestine, free lactose is fermented by
colonic bacteria to yield short-chain fatty acids and hydrogen gas. The combined increase in fecal
water, intestinal transit, and generated hydrogen gas accounts for the wide range of gastrointestinal
symptoms.
History in patients with lactose intolerance may include abdominal fullness/bloating, nausea,
abdominal pain, diarrhea, and flatulence.
The symptoms of irritable bowel syndrome (IBS) resemble those of lactose intolerance and
can easily be confused. Some patients with IBS can also have lactose intolerance. Restriction of
milk products in these patients may relieve the symptoms of IBS.
Congenital lactose intolerance is inherited as an autosomal recessive trait and is very rare.
Primary lactose intolerance is due to low levels of lactase, which develop after childhood.
Secondary, or acquired, lactase deficiency may develop in a person with a healthy small
intestine during episodes of acute illness. This occurs because of mucosal damage or from
medications. Some causes of secondary lactase deficiency are as follows: acute gastroenteritis,
giardiasis, ascariasis, Crohn disease, celiac sprue, tropical sprue, radiation enteritis, diabetic
gastropathy, carcinoid syndrome, whipple syndrome, HIV enteropathy, kwashiorkor, chemotherapy,
gastrinoma.
Diagnostics
Breath hydrogrn test. This is the diagnostic test of choice. Subjects are administered lactose
after an overnight fast, after which expired air samples are collected before and at 30-minute
intervals for 3 hours to assess hydrogen gas concentrations. A rise in breath hydrogen concentration
greater than 20 parts per million over the baseline after lactose ingestion suggests lactase
deficiency.
Dietary elimination. Resolution of symptoms with elimination of lactose-containing food
products and resumption of symptoms with the reintroduction are findings suggestive of lactose
intolerance.
 Small bowel biopsy. This is the criterion standard; however, it is invasive and rarely
performed. A major advantage is that it provides definitive information. Biopsy samples from the
small bowel are assayed for lactase activity. The biopsy results may be normal if deficiency is focal
or patchy. This is not readily available and is not usually necessary.
Treatment
Dietary adjustment is the primary form of therapy for patients with lactose intolerance. Advise
patients to reduce or restrict products containing lactose. Prehydrolyzed milk (LACTAID) is
available and is effective. Yogurt and fermented products, such as cheeses, are better tolerated than
regular milk. Soy-based milk or food products are well tolerated.
Commercially available lactase enzyme preparations (eg, LACTAID, Lactrase) are effective
in reducing symptoms; however, they may not be effective in some patients, partially due to
insufficient dosing.
Supplemental calcium should also be recommended. In secondary lactase deficiency,
treatment is directed at the underlying cause.

Celiac disease
Celiac disease (CD) is a multifactorial, autoimmune disorder that occurs in genetically
susceptible individuals. It is triggered by a well-identified environmental factor (gluten and related
prolamins), and the autoantigen is also well known (ie, the ubiquitous enzyme tissue
transglutaminase). The disease primarily affects the small intestine, where it progressively leads to
flattening of the small intestinal mucosa. Three cereals contain gluten and are toxic for patients with
celiac disease: wheat, rye, and barley.
The genetic susceptibility to celiac disease is conferred by well-identified haplotypes in the
human leukocyte antigen (HLA) class II region (ie, DR3 or DR5/DR7 or HLA DR4).
The classic celiac lesion occurs in the proximal small intestine with typical histological
changes of villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytosis.

Clinical picture
Currently, 4 possible presentations of celiac disease are recognized, as follows:
 Typical presentation: This presentation is primarily characterized by GI signs and symptoms.
 Atypical presentation: GI signs and symptoms are minimal or absent, and various extraintestinal
manifestations are present.
 Silent presentation: The small intestinal mucosa is damaged, and celiac disease autoimmunity can
be detected with serology; however, no symptoms are present.
 Potential presentation: Patients are symptomatic, and the mucosa morphology is normal. These
individuals have genetic compatibility with celiac disease and may also show positive
autoimmune serology. Full-blown celiac disease may develop at a later stage in some of these
individuals.

Typical presentation. The so-called typical form of celiac disease presents with GI symptoms
that characteristically appear at age 9-24 months. Symptoms begin at various times after the
introduction of foods that contain gluten. Infants and young children typically present with chronic
diarrhea, anorexia, abdominal distension, abdominal pain, poor weight gain or weight loss, and
vomiting. Severe malnutrition can occur if the diagnosis is delayed. Behavioral changes are
common and include irritability and an introverted attitude. Rarely, severely affected infants present
with a celiac crisis, which is characterized by explosive watery diarrhea, marked abdominal
distension, dehydration, hypotension, and lethargy, often with profound electrolyte abnormalities,
including severe hypokalemia. Older children with celiac disease who present with GI
manifestations may have onset of symptoms at any age. If gluten is introduced during breast
feeding, the symptoms tend to be less often. GI symptoms in older children are typically less
evident and include nausea, recurrent abdominal pain, bloating,constipation, and intermittent
diarrhea.
The main extraintestinal manifestations of celiac disease are as follows:
 Dermatitis herpetiformis: A blistering skin rash that involves the elbows, knees, and
buttocks are associated with dermal granular immunoglobulin (Ig) A deposits. Dermatitis
herpetiformis is a rare occurrence in childhood and is described almost exclusively in teenagers and
adults.
 Dental enamel hypoplasia: These enamel defects involve only the permanent dentition and
may be the only presenting manifestation of celiac disease. Often, GI symptoms are minimal or
absent.
 Iron-deficiency anemia: In several studies, iron-deficiency anemia that is resistant to oral
iron supplementation is reportedly the most common extraintestinal manifestation of celiac disease
in adults. However, in children, iron deficiency is seldom seen as the only presenting sign, although
the finding of anemia is common.
 Short stature and delayed puberty: Short stature may be the only manifestation of celiac
disease. As many as 10% of children with idiopathic short stature may have celiac disease that can
be detected on serologic testing. Some patients with short stature also have impaired growth
hormone production following provocative stimulation testing; this production returns to normal
when the patient is put on a gluten-free diet. Adolescent girls with untreated celiac disease may
have delayed onset of menarche.
 Chronic hepatitis and hypertransaminasemia: Patients with untreated celiac disease
commonly have elevated transaminase levels (alanine aminotransferase [ALT], aspartate
aminotransferase [AST]). As many as 9% of patients with elevated transaminase levels of unclear
etiology may have silent celiac disease. Liver biopsy findings in these patients reveal nonspecific
reactive hepatitis. In most cases, liver enzymes normalize on a gluten-free diet.
 Arthritis and arthralgia: Arthritis can be a common extraintestinal manifestation of adults
with celiac disease, including those on a gluten-free diet. As many as 3% of children with juvenile
chronic arthritis may have celiac disease.
 Osteopenia and osteoporosis: Approximately 50% of children and 75% of adults have a low
bone mineral density at the time of diagnosis; this low density reaches severe degrees, including
osteoporosis. Bone mineral density improves in most patients on gluten-free diet and returns to
normal as soon as 1 year after starting the diet in children. However, the response to the diet can be
much less marked in adults.
 Neurological problems: Numerous neurological conditions have been attributed to celiac
disease in adults and, to a lesser extent, in children. Celiac disease may cause occipital calcifications
and intractable epilepsy; these patients can be resistant to antiseizure medicines but can benefit from
a gluten-free diet if it is started soon after onset of seizures. The association with cerebellar ataxia is
well described in adults; the term gluten-induced ataxia has been proposed.
 Psychiatric disorders: Although a large number of behavioral problems and disorders (eg,
autism, attention deficit hyperactivity disorder) have been thought to be caused by celiac disease, no
evidence has been conclusive. However, celiac disease can be associated with some psychiatric
disorders, such as depression and anxiety. These conditions can be severe and usually respond to a
gluten-free diet.
 Subfertility or infertility: Although somewhat controversial, reports have indicated that as
many as 6% of women who experience infertility or repeated miscarriages have celiac disease.

Examination findings depend on extent of celiac disease.

 Dry mucosal membranes with vomiting or diarrhea indicate the degree of dehydration.
 Oral aphthae are more frequent than in normal population.
 Dental enamel hypoplasia is a highly specific but relatively uncommon finding.
 Bloating of the abdomen is a relatively common finding.
 Muscle wasting is an obvious but uncommon finding and is part of the malnutrition that
ensues because of the malabsorptive condition.
 Celiac disease may occur in asymptomatic individuals without any positive clinical
findings, as noted above.

Diagnostics
Duodenal mucosa histology changes in celiac disease (CD) are documented while on a
gluten-containing diet and are characterized by a progressive deterioration of the villous
architecture associated with a progressive increase in crypt length and density.
The IgA endomysium (EMA-IgA) and tissue transglutaminase (TTG-IgA) tests are both
highly sensitive and highly specific, with values for both parameters exceeding 96% in most
studies.

Treatment
Total lifelong avoidance of gluten ingestion is the cornerstone treatment for patients with
celiac disease (CD). Wheat, rye, and barley are the grains that contain toxic peptides. They should
be eliminated as completely as possible, although daily intake doses larger than 10 mg are likely
needed to cause mucosal reaction. GI symptoms in patients with symptomatic celiac disease who
adhere to a gluten-free diet typically resolve within a few weeks; these patients experience the
normalization of nutritional measures, improved growth in height and weight (with resultant normal
stature), and normalization of hematological and biochemical parameters.
Tests
1. The following aspect doesn’t belong to IBS development reasons:
А. Infectious
В. Psychoemotional
С. Alimentary
D. Allergic
2. UUC most typical clinical symptom is:
А. Hemocolitis
В. Subfebrile temperature
С. Abdominal pain
D. Nausea and vomiting
3. The following disorders lie on the basis of lactose intolerance development:
А. Proteolysis and absorption of proteins
В. Carbohydrates breakdown and absorption
С. Lipolysis and absorption of fats
D. Vitamins splitting and absorption
4. The following doesn’t belong to IBS clinical variants:
А. Constipation prevailing variant
В. Diarrhea prevailing variant
С. Abdominal pain prevailing variant
D. Chronic intoxication prevailing variant
5. UUC basic treatment includes:
А. 5-ASA drugs
В. Antidiarrheal drugs
С. Spasmolytics
D. Prokynetics
6. Celiac disease basic treatment is:
А. Replacing enzyme therapy
В. Gluten-free diet
С. Electrolyte balance correction
D. Immunomodulating therapy
Answers: 1-А, 2 – А, 3- В, 4- -D , 5- В, 6 -В
Tasks
Task №1
5 years old boy has been hospitalized complaining on fever, abdominal pain, frequent defecations
(10 – 12 times a day) with some admixture of mucous and blood in feces. Objective data: marked
signs of nonspecific intoxication and chronic anemization: weakness, paleness and icteritiousness.
Pain throughout large intestine, spastic bowel loops, enlarged and dense liver, splenomegaly are
detected in palpation. Intestinal discharges are fluid with macroscopic blood, mucous and puris.
Clinical blood test results: anemia, neutrophylic leukocytosis with a left shift, increased ESR.
Biochemical blood test: hypoproteinemia, hypoalbuminemia, CRP decrease, Fe and electrolytes
decrease. Coprogram: mucous, leukocytes and erythrocytes. Endoscopy: mucosa marked edema
and hyperemia, absence of vascular pattern, mucosa granularity, marked contact bleedings, single
erosions and erosive fields under fibrine and microabscesses.
Task:
1. Formulate the disgnosis and substantiate it.
2. Prescribe treatment.

Task №2
12 years old boy is followed up by psychiatrist during last 5 years. During last 4 years the boy
complains of constipations (intestinal discharges 1 - 2 times a week), feeling of incomplete
defecation, changes of excrement characteristics: it is dense, dry, sheep’s-like and ribbon. Objective
data: The skin is pink and clean. Abdomen is soft and painful throughout the colon in palpation,
spastic bowel loops are dtecetd. Liver is not enlarged. Endoscopy and US revealed no pathological
changes. Colonoscopy found out some pain in oxygen insufflation, mucosa vascular pattern
increase, high rigid folds of mucosa and increased tonus of natural sphincters.
Tasks
1. Formulate the diagnosis and substantiate it
2. Prescribe investigation plan
3. Prescribe necessary treatment
Answer: Acute UUC, moderate severity, active stage. Diet, 5-ASA drugs, anticholinergic drugs,
spasmolytics, sedative therapy, enzymes.

Answer. IBS: constipation prevailing variant. CBT, CUA, coprologic analysis, irrigography,
manometry. Unrefined products, enough quantity of ballast products in feeding ratio are
recommended. Bowel peristalsis stimulators (prokynetics), laxatives with hydrophylic effect should
be prescribed.