Malabsorption syndromes

are conditions that affect the digestion or the absorption of nutrients.

CLINICAL FEATURES

CLASSIFICATION : BASED ON THE PREDOMINANT NUTRIENT WHICH IS MALABSORBED

CLASSIFICATION BASED ON THE PREDOMINANT NUTRIENT WHICH IS MALABSORBED

CLINICAL APPROACH TO A CHILD WITH SUSPECTED MALABSORPTION

O/E: Signs of malnutrition Growth parameters Signs specific for the nutrient defecient:

Abnormal hair (Meknes hair)

Abdominal distention
Perianal excoriation


EVALUATION OF CHILDREN WITH SUSPECTED INTESTINAL MALABSORPTION 
In a child presenting with diarrhea, the initial work-up should includestool examination for:stool occult blood and leukocytes to exclude inflammatory disorders, stool microscopy and antibody tests for parasites such as Giardia, stool pH and reducing substance for carbohydrate malabsorption, and quantitative stool fat examination to identify fat malabsorption.A complete blood count includingperipheral smear for microcytic anemia,Macrocytic anemia folate &B12 lymphopenia (lymphangiectasia), neutropenia (Shwachman syndrome), and acanthocytosis (abetalipoproteinemia) is useful. S.albumin.serum immunoglobulin A (IgA) and tissue transglutaminase levels should be determined ,If celiac disease is suspected. Small bowel biopsy. Depending on the initial investigation results, more specific investigations can be planned.

FAT MALABSORPTION

a microscopic examination of stool for fat: mixing a small amount of stool with several drops of water or Sudan red stain. Fat droplets separate and can be easily identified, especially with a Sudan III stain. The presence of more than six to eight droplets per low-power field is abnormal. A positive testshould be confirmed with a 72-hr quantitative fecal fat test, which remains the gold standard for assessing steatorrhea. Excretion of more than 7% of the total fat intake is abnormal and suggests the presence of malabsorption.

CARBOHYDRATE MALABSORPTION

Clinitest reagent for reducing substances is a simple screening test and can be performed at the bedside. The test is easily performed by combining 10 drops of water with 5 drops of stool and then adding a Clinitest tablet. The color change can be quantified as trace to 4+ using a color sheet provided by the manufacturer. Only 2+ or higher should raise the possibility of sugar malabsorption. Sucrose is not a reducing sugar and requires hydrolysis with hydrochloric acid before analysis. Stool pH, obtained easily with pH paper, lower than 5.6 is also suggestive of carbohydrate malabsorption. The breath hydrogen test can also be used to evaluate carbohydrate malabsorption. The gas produced by bacterial degradation of carbohydrates is largely absorbed in the colon, enters the portal and systemic venous return, goes to the lung, and is then released in the breath

PROTEIN MALABSORPTION

Protein loss cannot be evaluated directly because bacterial protein accounts for such a large proportion of the stool nitrogen.Measurement of spot stool α1 -antitrypsin levels is helpful in establishing a diagnosis of protein-losing enteropathy. This serum protein is resistant to digestion and therefore can be measured in stool in contrast to albumin.

GLUTEN-SENSITIVE ENTEROPATHY (CELIAC DISEASE)

Celiac disease is an immune-mediated enteropathy caused by permanent sensitivity to gluten in genetically susceptible individuals which lead to mucosal damage. It is now estimated that the frequency of celiac disease in the United States is around 1:300

PATHOGENESIS. 

Celiac disease develops only after dietary exposure to the protein gluten, which is found in wheat, rye, oat and barley. The activity of gluten resides in the gliadin fraction



PATHOGENESIS: 
A genetic predisposition monozygotic twins approaching 100%. Two to 5% of first-degree relatives have symptomatic gluten-sensitive enteropathyIndividuals with HLA-DQ2 and –DQ8 tissue type are at higher risk. Celiac disease occurs at a higher frequency in children with type 1 diabetes and is 50 times more common Down syndrome.selective IgA deficiency.Turner syndrome, thyroiditis. Environmental factors such as viruses may also play a role

Total or subtotal villus atrophy, crypt hyperplasia, increased number of intraepithelial lymphocytes, damage to the surface epithelium in the small bowel. The injury is greatest in the proximal small bowel and extends distally for a variable distance.

A. SYMPTOMS AND SIGNS

A.

A. SYMPTOMS AND SIGNS

6. Constipation, vomiting, and abdominal pain—This triad of symptoms may in a small number of patients dominate the clinical picture and suggest a diagnosis of intestinal obstruction. Constipation generally results from a combination of anorexia, dehydration, muscle weakness, and bulky, fatty stools7.Short stature and delayed puberty are characteristic in older children

NONGASTROINTESTINAL MANIFESTATIONS OF CELIAC DISEASE

Dermatitis herpetiforms Dental enamel hypoplasia Osteopenia/osteoporosis Short stature Delayed puberty Anemia (nonresponsive to iron therapy, seen in adults only) Hepatitis Arthritis Brain calcifications Neurologic symptoms

LABORATORY FINDINGS

1.increase Fat content of stools—A 3-day collection of stools usually reveals excessive fecal fat. 2. Impaired carbohydrate absorption3. Hypoproteinemia —Hypoalbuminemia

SEROLOGIC TESTS

Antigliadin and antireticulin antibodies are often present in celiac disease. However, there is a 10% false-positive rate for the IgG antigliadin antibody among healthy individuals. Endomysial or tissue transglutaminase antibody assays are the most sensitive and specific screening tests for celiac disease. As both of these antibodies are of the IgA class, screening for them in a patient who is IgA deficient may yield a falsely negative screen result. The best available serologic screening test, therefore, is a quantitative IgA level with a transglutaminase or endomysial antibody assay.


GENETIC TESTS
have an increasing role in the diagnosis Less than 2% of celiac patients lack both HLA specificities; at the same time, approximately one third of the “normal” population has one or the other marker; that means that the measurement of HLA DQ2 and/or DQ8 has a strong negative predictive value but a very weak positive predictive value for the diagnosis of celiac disease. With these limitations the test can prove useful to exclude celiac disease when the genetic studies are negative in subjects on a gluten-free diet or in subjects belonging to an at-risk group (e.g., 1st-degree relatives, insulin-dependent diabetics, patients with Down syndrome) to avoid long-term follow-up.

D. BIOPSY FINDINGS Total or subtotal villus atrophy, crypt hyperplasia, increased number of intraepithelial lymphocytes, damage to the surface epithelium in the small bowel.

The ultimate diagnosis of celiac disease relies on the demonstration of specific, though not pathognomonic, histopathologic abnormalities in the small bowel mucosa .According to The European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) current criteria, the 2 requirements mandatory for the diagnosis of celiac disease are: the finding of villous atrophy with hyperplasia of the crypts and abnormal surface epithelium, while the patient is eating adequate amounts of gluten, and a full clinical remission after withdrawal of gluten from the diet. The finding of circulating IgA celiac disease–associated antibodies at the time of diagnosis and their disappearance on a gluten-free diet adds weight to the diagnosis. A control biopsy to verify the consequences of the gluten-free diet on the mucosal architecture is considered mandatory only in patients with an equivocal clinical response to the diet. Gluten challenge is not considered mandatory except in situations where there is doubt about the initial diagnosis, for example, when an initial biopsy was not performed or when the biopsy specimen was inadequate or atypical of celiac disease.

Differential DiagnosisThe differential diagnosis includes disorders that cause malabsorption. Strict adherence to two diagnostic criteria is essential—the characteristic small bowel microscopic changes and clinical improvement on a gluten-free diet. Repeated mucosal biopsies to prove histologic recovery on gluten-free diet and relapse on gluten challenge are not critical to the diagnosis in typical patients.

TreatmentA. DIETTreatment consists of dietary gluten restriction for life. All sources of wheat, rye, barley, and oat gluten must be eliminated during the initial treatment. Clinical improvement is usually evident within a week, and histologic repair is complete after 3–12 months. Tissue transglutaminase titers may decrease on a gluten free diet, but usually do not disappear.B. CORTICOSTEROIDS are indicated only in very ill patients with signs and symptoms of celiac crisis (profound malnutrition, diarrhea, edema, abdominal distention, and hypokalemia).

PROGNOSIS

Clinical and histologic recovery is the rule but may be slow. Malignant lymphoma of the small bowel occurs with increased frequency in adults with long-standing disease. Dietary treatment seems to decrease the risk of this complication.


CF, an autosomal recessive disorder, In the U.S., 1 in 3200 white newborns is born with CF The gene for CF, localized to the long arm of chromosome 7, termed cystic fibrosis transmembrane regulator (CFTR) The secretory and absorptive characteristics of epithelial cells are affected. the respiratory epithelium exhibits marked impermeability to chloride and an excessive reabsorption of sodium. These lead to a relative dehydration of the airway secretions, resulting in impaired mucociliary transport and airway obstruction

THE CLASSIC HALLMARK OF CF:

Most patients are colonized with Haemophilus influenzae, Staphylococcus aureus, or Pseudomonas aeruginosa or Burkholderia cepacia cough (the most common initial pulmonary manifestation), sputum production, hyperinflation, bronchiectasis, and pulmonary insufficiency and death. Digital clubbing is common, even without significant lung disease. Chronic sinusitis is nearly universal, and nasal polyposis is common. Other potential pulmonary complications of CF include atelectasis, progressive bronchiectasis, hemoptysis, and pneumothorax

PANCREATIC INSUFFICIENCY

Most patients with CF have exocrine pancreatic insufficiency early in life (if not at birth) as a result of inspissation of mucus in the pancreatic ducts. Maldigestion with secondary malabsorption results in steatorrhea (large, fatty, floating, foul-smelling stools) and many secondary deficiency states (vitamins A, D, E, and K) in untreated patients. Nutrient malabsorption also results in failure to thrive despite a ravenous appetite.

In adolescent or adult patients, relative insulin deficiency may develop. Hyperglycemia and CF-related diabetes may become symptomatic; ketoacidosis is rare.


Secondary amenorrhea Women with CF have given birth, however. Males are almost universally azoospermic, with atrophy or absence of the vas deferens. The failure of the sweat ducts to conserve salt may lead to heat exhaustion or to unexplained hypochloremic alkalosis in infants.

Diagnostic Criteria for Cystic Fibrosis (CF)

Presence of typical clinical features (respiratory, gastrointestinal, or genitourinary)
OR
A history of CF in a sibling
OR
A positive newborn screening test
PLUS
Laboratory evidence for CFTR dysfunction:
Two elevated sweat chloride concentrations obtained on separate days
OR
Identification of two CF mutations
OR
An abnormal nasal potential difference


SWEAT TEST
The sweat test, which involves using pilocarpine iontophoresis to collect sweat and performing chemical analysis of its chloride content, is the standard approach to diagnosis of CF. The procedure requires care and accuracy. An electric current is used to carry pilocarpine into the skin of the forearm and locally stimulate the sweat glands. If an adequate amount of sweat is collected, the specimens are analyzed for chloride concentration. Testing may be difficult in the 1st 2 wk of life because of low sweat rates but is recommended any time after the 1st 48 hr of life. Positive results should be confirmed; for a negative result, the test should be repeated if suspicion of the diagnosis remains. a positive result obtained from a sweat test on two or more occasions (positive if >60 mEq/L with adequate sweat collection of at least 75 mg, borderline if 40 to 60 mEq/L, and negative if <40 mEq/L


Non-CF conditions associated with elevated concentrations of sweat electrolytes(false +ve) include untreated adrenal insufficiency, ectodermal dysplasia, hereditary nephrogenic diabetes insipidus, hypothyroidism, hypoparathyroidism, familial cholestasis, pancreatitis, mucopolysaccharidoses, and malnutrition. Most of these conditions can be easily distinguished from CF by clinical criteria False-negative test results may be encountered in children with hypoproteinemic edema.

TREATMENT :