Clinical Presentation, Diagnosis and Treatment of Celiac Disease

Celiac disease immune mediated disease in which the body makes antibodies against tissue transglutaminase (tTG) enzyme. Gluten is the most important environmental trigger and the disease has specific association with class II haplotypes of HLA DQ2 (haplotypes DR17 or DR5 or 7) and, DQ8 (haplotype DR4).


Clinical presentation: Typically it presents with abdominal symptoms between 6 months to 2 years of age (Age at which gluten is introduced in the diet). Symptoms include diarrhea, poor appetite, abdominal pain, emesis and failure to thrive. Celiac crisis can be a rare presentation in which the patient has severe watery diarrhea, bloating, dehydration, electrolyte imbalance(low K) and shock. Older children can present with nausea, vomiting, recurrent stomachache, constipation, diarrhea, anemia and stunting of growth.


Diagnosis: Antigliadin (AGA) tests were commonly used but now have fallen out of favor due to low sensitivity and specificity. The IgA endomysium (EMA-IgA) and tissue transglutaminase (TTG-IgA) tests are currently the tests of choice due to their high specificity. Diagnosis has to be confirmed by duodenal biopsy A minimum of 4 biopsy samples are recommended as patchy involvement is common.


Treatment: Complete avoidance of gluten is the key. This means avoiding Wheat, rye, barley. Oats are considered safe.

Pseudomembranous colitis (PMC)/Clostridium Difficile Infection

PMC is caused by Clostridium difficile which is a spore producing gram positive rod/bacillus. It's incidence is about 0.5% in hospitalized adults. PMC typically occurs in setting of altered gut flora due to antibiotics.

Common antibiotics impicated include: Clindamycin, Ciprofloxacin (and other fluoroquinolones), Cephalosporins and macrolides. Both Vancomycin and Metronidazole which are used in treatment of PMC can also cause PMC. Omeprazole(and other proton pump inhibitors) and chemotherapeutic drugs have also been shown to increase risk for PMC.

Treatment is typically done with oral metronidazole (Flagyl) or oral vancomycin. Of the two metronidazole is usually preferred because it is relatively inexpensive and to reduce the risk of developing vancomycin resistant enterococci (VRE) organisms.

Salmonella infection in humans

Salmonella infections occur mainly via ingestion of contaminated food. Ingested bacteria are usually killed by the acid in the stomach but when they do survive they can cause enteritis. Certain conditions that reduce the acidity in the stomach predispose to infection (e.g.infants, H2 pr Proton pump inhibitor use and pernicious anemia). It has been predicted that about one million organisms need to be ingested to cause infection.

Infection manifests with fever, loose stools, vomiting, dehydration and cramping pain.

Treatment 

Salmonella enteritis is usually self-limiting and does not need antibiotic therapy. Fluid management and symptoms control are the mainstay of the treatment.

However, antibiotics may be indicated in the following high risk groups:

Infants especially in the first 3 months of life
Elderly
Immunocompromised hosts
Individuals with prosthetic heart valves or joints

Salmonella is sensitive to a variety of antibiotics including fluoroquinolones(ciprofloxacin, ofloxacin, levofloxacin), azithromycin, trimethoprim/sulfamethoxazole(Bactrim/Septran) or amoxicillin.

Carrier state

Carrier state is defined as having positive stool cultures for >12 months. It can occur in 1 in about every 200 patients with salmonella enteritis. The bacteria resides in the biliary tree. Chronic antibiotic therapy (Ampicillin) or surgery is needed.

Pyogenic Liver(hepatic) Abscess

Pyogenic liver abscesses are usually secondary to peritonitis due to that subsequently spread to liver via the portal circulation or bile ducts. Other common form is as a result of hematogenous seeding in the setting of sepsis.

Clinical manifestations: fever, abdominal pain, nausea, vomiting, anorexia, weight loss and malaise.

Diagnosis of pyogenic liver abscess is confirmed by imaging (ultrasound r CT) followed by aspiration and culture of the abscess material. Most pyogenic liver abscesses are polymicrobial. Serology is useful in distinguishing pyogenic abscess from an amebic abscess.

Indications for drainage(less than 5cm usually aspiration is sufficient, greater than 5cm usually need in dwelling catheter):

- Loculated abscesses

- Abscesses with viscous contents obstructing drainage catheter

- Underlying disease requiring primary surgical management

- Inadequate response to percutaneous drainage within seven days
- Multiple abscesses (depends on number, position, and size)

Antibiotics:
A total of 4-6 weeks of therapy is needed.


Options for empiric gram-negative and anaerobic coverage include:

1) Penicillin derivatives: Ampicillin-sulbactam, Piperacillin/tazobactam or Ticarcillin-clavulanate
2) Cephalosporins: Ceftriaxone with metronidazole
3) Fluoroquinolone: Ciprofloxacin or Levofloxacin with metronidazole
4) Carbapenems: Imipenem, Meropenem or Ertapenem

Enteropeptidase

Enteropeptidase is a pancreatic enzyme needed for the conversion of Trypsinogen to Trypsin inthe small intestine. Deficiency of this enzyme will lead to diarrhea, growth retardation, hypoalbuminemia and edema due to protein malabsorption.

Inflamatory Bowel Disease

	Crohn's disease	Ulcerative colitis
Terminal ileum involvement	Commonly	Seldom
Colon involvement	Usually	Always
Rectum involvement	Seldom	Usually
Involvement around the anus	Common	Seldom
Bile duct involvement	No increase in rate of primary sclerosing cholangitis	Higher rate
Distribution of Disease	Patchy areas of inflammation (Skip lesions)	Continuous area of inflammation
Endoscopy	Deep geographic and serpiginous (snake-like) ulcers	Continuous ulcer
Depth of inflammation	May be transmural, deep into tissues	Shallow, mucosal
Fistulae	Common	Seldom
Stenosis	Common	Seldom
Autoimmune disease	Widely regarded as an autoimmune disease	No consensus
Cytokine response	Associated with Th1	Vaguely associated with Th2
Granulomas on biopsy	Can have granulomas	Granulomas uncommon
Surgical cure	Often returns following removal of affected part	Usually cured by removal of colon
Smoking	Higher risk for smokers	Lower risk for smokers