Download Latent coeliac disease

Fifth stage
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Pediatric
Lec. 2
15/3/2017
CHRONIC DIARRHOEA
• chronic or persistent diarrhea is defined as an episode that lasts
longer than 14 days.
• four principle pathophysiologic mechanisms: osmotic, secretory,
dysmotility associated, and inflammatory
1- Osmotic diarrhea is caused by a failure to absorb a luminal solute,
resulting in secretion of fluids and net water retention across an osmotic
gradient(best exemplified by the common disorder of lactose
malabsorption) , either because of dissacharidase deficiencies or
because the absorptive capacity of the intestine for that sugar may be
overwhelmed by excessive consumption, eg, fructose and sorbitol. Such
excessive intake may be seen in young children drinking fruit juices
2- Secretory diarrhea occurs when there is a net secretion of electrolyte
and fluid from the intestine without compensatory absorption, Children
with a pure secretory diarrhea will therefore continue to experience
diarrhea even while fasting. (Congenital chloride diarrhea)
3- Chronic diarrhea associated with intestinal dysmotility typically
occurs in the setting of intact absorptive abilities. Intestinal transit time
is decreased, the time allowed for absorption is minimized, and fluid is
retained within the lumen(diarrhea-predominant irritable bowel
syndrome (IBS))
4- Inflammatory diarrhea (may encompass all of the pathophysiologic
mechanisms) . Inflammation with resultant injury to the intestine may
lead to malabsorption of dietary macronutrients which, in turn, creates a
luminal osmotic gradient. Additionally, particular infectious agents may
induce secretion of fluid into the lumen, and blood in the gut may alter
intestinal motility. Diseases such as inflammatory bowel disease (IBD)
and celiac disease
AETIOLOGY:
1- Enteric infections are by far the most frequent cause of chronic
diarrhea, both in developing and industrialized countries
Other cause in the developing countries is Entamoeba histolytica
Giardiasis:
 Giardia is a protozoal parasite which is infective in the cyst form.
 lt also exists in the trophozoite form and is found in contaminated
food and water.
 Clinical manifestations vary; can be asymptomatic, acute
diarrhoeal disease, chronic diarrhoea.
 Partial villous atrophy is occasionally seen
 Diagnosis is by stool examination for cysts or examination of the
duodenal aspirate at small-bowel biopsy
 Treatment is with metronidazole
Amoebiasis:
 Caused by Entamoeba histolytica, a protozoan, excreted as cysts
or trophozoites in stool of infected patients
 Faecal-oral transmission of cysts
Clinical manifestations
 Intestinal disease - asymptomatic or mild symptoms, e.g.
abdominal distension,flatulence, constipation, loose stools ,
 Acute amoebic colitis (dysentery) - abdominal cramps, tenesmus,
diarrhoea with blood and mucus - complications include toxic
megacolon, fulminant colitis, ulceration and, rarely, perforation
 Extraintestinal disease:Liver abscess - acute ::fever, abdominal
pain and liver tenderness, or subacute with weight loss and vague
abdominal symptoms; rupture of the abscess into the abdomen or
chest may occur Rarely, abscesses in the lung, pericardium, brain
and genitourinary tract
Diagnosis
 Microscopy of stool, biopsy specimens and aspirates, serology if
extraintestinal disease
Treatment
To eliminate the tissue-invading trophozoites as well as cysts
Metronidazole followed by a luminal amoebicide, e.g. paromomycin
2- Lactose intolerance or carbohydrate malabsorption may be caused
by a brush-border enzyme defect in lactase(primary rare) or other
enzymes--More commonly, lactose intolerance is secondary to lactase
deficiency caused by intestinal mucosal damage((celiac disease,
rotavirus infection) and is usually transient, improving with mucosal
healing
Unabsorbed carbohydrates enter the large bowel and are fermented by
intestinal bacteria, producing organic acids and gases
Features: explosive watery diarrhea, flatulence, abdominal distention,
and pain,,perianal excoriation---may lead to weight loss
Investigations:
1- An acidic stool with >2+ reducing substance suggests carbohydrate
malabsorption(clinitest tablets).
2- Breath hydrogen test is used to identify the specific carbohydrate
that is malabsorbed. After an overnight fast, the suspected sugar
(lactose, sucrose, fructose, or glucose) is administered as an oral solution
(carbohydrate load 1-2 g/kg, maximum 50 g).
In malabsorption, the sugar is not digested or absorbed in the small
bowel, passes on to the colon, and is metabolized by the normal bacteria
flora.
One of the products of this process is hydrogen gas, which is absorbed
through the colon mucosa and excreted in the breath.
Increased hydrogen concentration in the breath samples suggests
carbohydrate malabsorption.
• A rise in breath hydrogen of 20 ppm above the baseline is
considere a positive test.
• The child should not be on antibiotics at the time of the test,
because colonic flora is essential for fermenting the sugar
3- Small bowel mucosal biopsies can measure mucosal disaccharidase
(lactase) concentrations directly.
Treatment:: A lactose-free formula (based on either soy or cow's
milk) can be used in infants.
In older children, low-lactose milk can be consumed.
Addition of lactase to dairy products usually abbreviates the
symptoms.
Live-culture yogurt contains bacteria that produce lactase enzymes
and is therefore tolerated in most patients with lactase deficiency.
Hard cheeses have a small amount of lactose and are generally well
tolerated
3- Allergy to cow’s milk protein and other food proteins also may
present during infancy with chronic diarrhea
Clinical spectrum of cows' milk protein intolerance:
A- Acute type 1 -mediated hypersensitivity(10 MINT—2 HOURS)
B- Delayed-onset hypersensitivity(48-72 HOURS)
C- Cows-milk-sensitive enteropathy( chronic diarrhea with
malabsorption)
D- Cows'milk allergic colitis( BLOODY DIARRHOEA)
E- Non-specific symptoms possibly attributable to cows milk
colic, generalized irritability, chestiness, recurrent upper respiratory
tract symptoms and constipation
Diagnosis is dependent on the clinical manifestations. A good history
and, if possible, dietetic assessment is essential. To strictly diagnose
allergy the Goldmann criteria should be met, which are that the
attributable symptoms disappear on removal of the offending
antigen and recur when it is reintroduced.
MANAGEMENT:
 Milk exclusion with a milk substitute.
 Soya preparations are commonly used and are palatable.
 There is, however, a cross-reactivity between cows' milk and soya
protein of up to one-third and so hydrolysed protein formula
feeds 'are preferred.
 Soya products should not be used in infants < 6 months
 The natural history of cows' milk intolerance is one of resolution
with 80-90% back on a normal diet by their third birthday
 Children with a past history of anaphylaxis or severe respiratory
symptoms following allergen ingestion require an adrenaline pen
for use either in the home or school setting in the event of
accidental exposure to the offending food antigen
 It is common in children with milk allergy to see reactions to other
foods, the most common of which are soya, egg, wheat and
peanut.
 Skin-prick testing and IgE RAST testing are most useful in children
with peanut, nut and egg allergy.
4- Chronic diarrhea may be the manifestation of maldigestion caused
by exocrine pancreatic disorders. In most patients with cystic fibrosis,
exocrine pancreatic insufficiency results in steatorrhea and protein
malabsorption
Cystic fibrosis:
Cystic fibrosis (CF):: is the commonest lethal recessive disease of
Caucasians. The gene responsible encodes CF transmembraneconductance regulator (CFTR) and is on chromosome 7.
The primary function of CFTR is as a chloride-ion channel, but it also
inhibits the epithelial sodium channel.
CF respiratory epithelium therefore fails to secrete chloride ions (fails
to absorb in the sweat gland, hence high sweat electrolytes), and
hyperabsorbs sodium ions and thus HzO, dehydrating the airway
surface.
Secretions are viscid, impairing mucociliary clearance and thus host
defence.
Presentation:
Neonatal ::Commonest presentation is with meconium ileus—
prolonged jaundice
Pulmonary:: recurrent chest infections—allergic bronchopulmonary
aspergellosis—cor pulmonale
Extrapulmonary involvement:Pancreas Exocrine insufficiency
Presents with steatorrhoea and faltering growth
Treat with pancreatic enzyme supplements (e.g, Creon)
others: D.M—liver disease—sinusitis—infertility—meconium ileus
equivalent
5- The most benign etiology of chronic diarrhea is nonspecific
diarrhea that encompasses functional diarrhea (or toddler’s
diarrhea) in children younger than 4 yr of age and irritable bowel
syndrome in those 5 yr of age and older. The diseases fall under the
umbrella of functional disorders, in that in older children abdominal
pain is often associated with diarrhea alternating with constipation
and growth and weight gain are normal
6- In older children and adolescents, inflammatory bowel diseases,
including Crohn disease, ulcerative colitis cause chronic diarrhea
that is often associated with abdominal pain, elevated inflammatory
markers
7- Diarrhea may be the result from an excessive intake of fluid and
carbohydrate(fruit juice). If the child’s fluid intake were >150
mL/kg/24 hr, fluid intake should be reduced not to exceed 90
mL/kg/24 hr
8- A reduction of intestinal absorptive surface is responsible for
diarrhea in celiac disease, a genetically determined permanent
gluten intolerance that affects as many as 1 in 100 individuals,
depending on geographic origin. In the genetically susceptible host,
gliadin, the major protein of gluten, reacts with the immune system
to cause villous atrophy. The reduction of functional absorptive
surface area is reversible upon restriction of gluten from the diet.
• There are associations with HLA DQ2 and DQ8.
• There is an increased incidence in first-degree relatives
(approximately 1 : 10)
Coeliac disease presents after 6 months of age (i.e. after gluten has been introduced
into the diet). Chronic diarrhoea and poor weight gain (short stature in older children)
generally occur. Other features include anorexia, lethargy, generalized irritability,
abdominal distension and pallor
DIAGNOSIS:
Diagnosis is based on positive serology, small bowel biopsy with characteristic
histology and response to treatment within 2–4 weeks.
Serological testing
IgA TTG (tissue transglutaminase) is currently the first-line investigation of choice for
guiding diagnosis. It has very high accuracy .
IgA levels are routinely performed in all patients because those with low IgA levels
can be falsely negative (IgA deficiency is very common). This group should have IgG
to TTG measured.
Small bowel biopsy
All children with a positive serological test should have small bowel biopsies to
confirm the diagnosis before starting a gluten-free diet
The characteristic features on biopsy are of subtotal villous atrophy, crypt
hypertrophy, intraepithelial lymphocytosis and a lamina propria plasma-cell infiltrate
Other investigations
HLA-DQ2 or -DQ8 can be considered in specific clinical situations where there is
uncertainty in the diagnosis
Differential diagnosis of partial villous atrophy:
• Coeliac disease
• Cows’ milk protein sensitive enteropathy
• Soy protein-sensitive enteropathy
• Eosinophilic gastroenteritis
• Gastroenteritis and post-enteritis syndrome
• Giardiasis
• Small bowel bacterial overgrowth
• Inflammatory bowel disease
• Immunodeficiency
• Intractable diarrhoea syndromes, e.g. autoimmune enteropathy
• Drugs, e.g. cytotoxics
• Radiotherapy
TREATMENT
The only treatment for celiac disease is lifelong strict adherence to a
gluten-free diet .This requires a wheat-, barley-, and rye-free diet
There is a long-term risk of small-bowel lymphoma and other
gastrointestinal malignancies if the diet is not adhered to
Gluten challenge:
There are two common indications for a formal gluten challenge:
1. Patients presenting having restricted or excluded gluten from their
diet before the diagnosis being confirmed
2. If the diagnosis of coeliac disease is made at age <2 years and there is
any doubt about the full diagnostic criteria being met, a formal gluten
challenge should at least be considered.
• Gluten challenge involves a period of adequate gluten
reintroduction (10–15 g gluten/day), usually at 6 weeks to 3
months, under the supervision of a dietician. Symptomatic relapse
may occur rapidly or after many months and patients should be
followed with serial serological testing with biopsy once serology
becomes positive.
Silent coeliac: disease refers to seropositivity with histological
evidence of villous atrophy in keeping with a diagnosis of coeliac
disease in an asymptomatic individual.
Latent coeliac disease refers to seropositivity in the absence of
histological changes in the small bowel mucosa to meet the
diagnostic criteria for coeliac disease. A significant number of these
patients will go on to develop the mucosal changes associated with
coeliac disease and its clinical consequences.
Coeliac crisis: is a rare complication of coeliac disease characterized
by explosive diarrhoea, abdominal distension, dehydration and
electrolyte disturbance with hypoalbuminaemia, which may
necessitate treatment with steroids during the initial phase.
Conditions with an increased prevalence of coeliac disease:
• Type 1 diabetes
• Autoimmune thyroiditis
• Down syndrome
• Turner syndrome
• William syndrome
• Selective IgA deficiency
• First-degree relatives
Malabsorption:
Disorders affecting the digestion or absorption of nutrients
Presentation
• Diarrhoea.
• Steatorrhoea((difficult to flush down the toilet and has an odor which
pervades the whole house,pale,bulky)
• Flatulence.
• FTT/weight loss.
• Muscle wasting.
• Abdominal distension.
• Peri-anal excoriation.
• Delayed puberty.
• Features of underlying illness, e.g. abdominal pain in Crohn’s disease.
• Signs of nutritional deficiency states, e.g. ascites due to
hypoalbuminaemia
Investigations:
Initial screening tests should include: FBC; U&E; creatinine; albumin;
total protein; Ca2+; PO4 3– ; LFT; iron status, coeliac antibody screen;
coagulation screen, stool M,C&S.
FBC:full blood count
U&E: urea and electrolytes
LFT: liver function test
Stool M,C&S: stool microscopy –culture and sensitivity
If diagnosis still unclear, consider:
• Upper GI endoscopy with biopsy to look for an enteropathy,
ileocolonoscopy if features suggest colitis (ensure clotting screen normal
before procedure).
• Sweat test.
• Immune function tests.
• Faecal fat measurement.
• Faecal elastase.
• Faecal A1-antitrypsin.
• Exocrine pancreatic function tests.
Treatment:
• Treat underlying disease, e.g. metronidazole for giardiasis, gluten-free
diet for coeliac disease.
• Supplemental digestive enzymes, e.g. pancreatic enzymes in cystic
fibrosis.
• Nutritional supplements to correct deficiencies.
• PN if malabsorption severe or slow to recover.