Objectives of this lecture:
1.What’s celiac disease?2.What’s acrodermatitis enteropathica?
3.What’s intestinal lymphangiectasia?
4. Cystic Fibrosis
5.DDx of constipation
6.DDx of recurrent abdominal pain
• Coeliac disease( Gluten-Sensitive Enteropathy GSE )
• It is an enteropathy in which the gliadin fraction of gluten provokes a damaging immunological response in the proximal small intestinal mucosa. As a result, the rate of migration of absorptive cells moving up the villi (enterocytes) from the crypts is massively increased but is insufficient to compensate for increased cell loss from the villous tips. Villi become progressively shorter & then absent, leaving a flat mucosa.• The incidence 1:3000. It is considered an autoimmune condition because of the presence of anti–TG2 antibodies & the association with other autoimmune diseases (thyroid, liver, diabetes, adrenal).
• It is triggered by the ingestion of wheat gluten and related prolamines from rye & barley.
• A genetic predilection is suggested by the family aggregation & the concordance in monozygotic twins, which approaches 100% but environmental factors might affect . Prolonged breastfeeding has been associated with ↓ incidence of symptomatic disease.
• classical presentation is at 8-24 months of life with:
• FTT following introduction of gluten in cereals
• General irritability
• Abnormal stools(steatorrheal i.e. offensive greasy or not)
• Abdominal distension and buttock wasting
• Increasingly, children may present in later childhood with:
• anemia (iron and/or folate deficiency), growth failure or short stature, with little or no GIT symptoms.
• Occasionally constipation, rectal prolapse, or intussusception.
Celiac patient
• Diagnosis :• Serologic tests have a crucial role in Dx
IgA anti- tissue transglutaminase TG2 [sensitivity is ˷ 87%, specificity is ˷ 95%).
Some 10% of pts who diagnosed earlier than 2 yr of age show absence of IgA anti-TG2. For them, the measurement of :
serum antigliadin Ab is generally advised. Ab against gliadin-derived deamidated peptides (D-AGA) have been assessed.
A problem with serology is represented by the association of celiac disease with IgA deficiency. Serum IgA should always be checked, & in this case D-AGA, IgG anti-endomysium, or TG2 should be sought.
Negative serology should not preclude a biopsy examination when the clinical suspicion is strong.
• Confirmation depends upon:
• demonstration of a flat mucosa on jejunal biopsy followed by the resolution of symptoms & catch-up growth upon gluten withdrawal. {There is no place for the empirical use of a gluten-free diet as a diagnostic test for coeliac disease in the absence of a jejunal biopsy.}• OTHER CAUSES OF FLAT MUCOSA:
• Tropical sprue
• Giardiasis
• Cow's milk & soy protein enteropathy…….etc
• Silent celiac disease( No apparent symptoms in spite of histological evidence of villous atrophy) is being increasingly recognized, mainly in asymptomatic 1st-degree relatives of celiac pts .
• Treatment :
• The only treatment for celiac disease is lifelong strict adherence to a gluten-free diet
• Screening for celiac disease is indicated in :
• DM type 1
• Down ,Turner & William syndromes
• Unexplained IDA
• 1st-degree relatives
• Autoimmune thyroiditis, Addison disease
• Dermatitis herpetiformis
• Short stature
• Unexplained osteoporosis
Acrodermatitis Enteropathica
is a rare AR disorder caused by an inability to absorb sufficient zinc from the diet.The genetic defect is in the intestinal zinc specific transporter gene . Initial signs and symptoms usually occur in the first few months of life, often after weaning from breast milk to cow's milk.
The cutaneous eruption consists of vesiculobullous, eczematous, dry, scaly, or psoriasiform skin lesions symmetrically distributed in the perioral, acral, perineal areas & on the cheeks, knees, and elbows .
• The hair often has a peculiar, reddish tint, & alopecia of some degree is characteristic.
• Ocular manifestations include photophobia, conjunctivitis, blepharitis, and corneal dystrophy detectable by slit-lamp examination.
• Associated manifestations include chronic diarrhea, stomatitis, glossitis, paronychia, nail dystrophy, growth retardation, irritability, delayed wound healing, intercurrent bacterial infections, and superinfection with Candida albicans. Lymphocyte function and free radical scavenging are impaired.
• Without Rx, the course is chronic and intermittent but often relentlessly progressive. When the disease is less severe, only growth retardation and delayed development may be apparent.
Acrodermatitis enteropathica
• Dx• established by the constellation of clinical findings and detection of a low plasma zinc concentration. Histopathologic changes in the skin are nonspecific
• Rx
• Oral zinc compounds is the treatment of choice. Optimal doses range from 50 mg/24 hr of zinc sulfate, acetate, or gluconate daily for infants up to 150 mg/24 hr for older children.
• DDx: secondary zinc deficiency
Intestinal Lymphangiectasia
Obstruction of the lymphatic drainage of the intestine can be due to either congenital defects in lymphatic duct formation or to 2ry causes .The congenital form is often associated with lymphatic abnormalities elsewhere in the body, as occur with Turner, Noonan, and Klippel-Trenaunay-Weber syndromes.
Causes of secondary lymphangiectasia include:
constrictive pericarditis
heart failure
retroperitoneal fibrosis
abdominal T.B
retroperitoneal malignancies
• Lymph rich in proteins, lipids, and lymphocytes leaks into the bowel lumen, resulting in protein-losing enteropathy, steatorrhea, and lymphocyte depletion.
• Hypoalbuminemia, hypogammaglobulinemia, edema, lymphopenia, malabsorption of fat and fat-soluble vitamins, & chylous ascites often occur.
• Dx
• suggested by the typical findings + elevated fecal α1-antitrypsin clearance.• Radiologic findings of uniform, symmetric thickening of mucosal folds throughout the small intestine are characteristic but nonspecific.
• Small bowel mucosal biopsy can show dilated lacteals with distortion of villi & no inflammatory infiltrate.
Rx
includes restricting the amount of long-chain fat ingested & administering a formula containing protein and medium-chain triglycerides (MCTs).
Supplementing a low-fat diet with MCT oil in cooking is used in the management of older children.
Rarely, parenteral nutrition is required. If only a portion of the intestine is involved, surgical resection may be considered.
Cystic Fibrosis (CF)
• AR disorder, the most common life-limiting genetic disease.
• The gene for CF, localized to the long arm of chrom 7, is a large gene that encodes a polypeptide termed cystic fibrosis transmembrane regulator (CFTR) is mutated causing dysfunctional epithelial transport & leading to CF.• The secretory and absorptive characters of epithelial cells are affected.
• Most pts 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 2ry malab steatorrhea & many 2ry def. states (vit A, D, E, & K) in untreated pt.
• This is in addition to chronic chest infection, finger clubbing & other respiratory symptoms.
• About 10% of pts are born with intestinal obstruction resulting from inspissated meconium (meconium ileus).
• In older patients, intestinal obstruction may occur because of maldigestion and thick mucus in the intestinal lumen (distal intestinal obstruction syndrome”DIOS”).
• DX
• a positive quantitative chloride sweat test (Cl− ≥ 60 mEq/L) in conjunction with 1 or more of the following features:
• typical chronic obstructive pulmonary disease
• documented exocrine pancreatic insufficiency
• a positive family history.
• Newborn Screening:
• immunoreactive trypsinogen results & limited DNA testing on blood spots, which are then coupled with confirmatory sweat analysis.• Rx of Intestinal Complications:
• pancreatic enzyme replacement
• When meconium ileus is suspected, a NGT is placed for suction & the newborn is hydrated. In many cases, gastrografin enemas with reflux of contrast material into the ileum not only confirm the Dx but have also resulted in the passage of a meconium plug and clearing of the obstruction.
Constipation
• Any definition of constipation is relative & depends on stool consistency, stool frequency, & difficulty in passing the stool.
• A normal child might have a soft stool only every 2nd or 3rd day without difficulty; this is not constipation.
• A hard stool passed with difficulty every 3rd day should be treated as constipation.
• Constipation can arise from defects either in filling or emptying the rectum . other definitions( Passage of hard scybalous pebble like or cylindrical cracked stools, Straining or painful defecation).
• DDx:
• Functional constipation• Anal & rectal diso.( anal fissure,anal stenosis, Imperf. anus…)
• Neurological/ neuromuscular( Hirschsprung dis,CP,Down )
Metabolic &endocrine(hypothyroidism,hypoK,hyperCa,DI)
• Medications(anticholinergics,antihistamines,opiods….)
• Toxins(lead poisoning, botulism…..)• Miscellaneous( CMPA,celiac disease…..)
• Abdominal Pain
• is one of the most common symptoms in children & adolescents & is estimated to account for ˷ 5% of unscheduled office visits.• Recurrent abdominal pain (RAP) as a recognizable entity in childhood was first characterized by pain that occurs at least three times over a period of 3 or more months severely enough to affect daily activities in children older than 3 years.
• Causes of recurrent or chronic abdominal pain:
• Associated with upper GI symptoms:
• GERD
• Peptic ulcer
• Crohn disease
• Henoch-Schonlein purpura
• Parasitic infection (Giardia)
• Motility disorders:
• Idiopathic gastroparesis
• Associated with altered bowel pattern:
• inflammatory bowel disorders(UC,CD idiopathic)• Parasitic
• Bacterial (C. difficile, Yersinia, Campylobacter,TB)
• Lactose intolerance
• Chronic constipation
• Neoplasia (lymphoma)
• Psychiatric disorders such as anxiety
• Presenting as isolated paroxysmal abdominal pain:
• Obstructive disorders• Small bowel lymphoma
• Postsurgical adhesions
• Abdominal migraine
• Acute intermittent porphyria
• Vascular disorders
• Mental disorders (school phobia)
• Functional abdominal pain
• Others
• Chronic pancreatitis
• Sickle cell crisis
• Chronic hepatitis
• Chronic cholecystitis & Choledochal cyst
• UPJ obstruction & Hydronephrosis
• Familial Mediterranean fever
Surgical:
Meckel's diverticulum
Recurrent intussusception
Internal, inguinal, or abdominal wall hernia
Chronic appendicitis
• The alarming signs & symptoms that suggest organic rather than functional causes for RAP:
• involuntary weight loss
• deceleration of linear growth
• GIT blood loss
• significant vomiting, chronic severe diarrhea
• persistent right upper or right lower quadrant pain
• unexplained fever
• family history of inflammatory bowel disease & etc..