Gastrointestinal, Liver and Nutritional Problems in Fanconi Anemia
Gastrointestinal, Liver and Nutritional Problems in Fanconi Anemia
Gastrointestinal, Liver and Nutritional Problems in Fanconi Anemia
Create successful ePaper yourself
Turn your PDF publications into a flip-book with our unique Google optimized e-Paper software.
<strong>Gastro<strong>in</strong>test<strong>in</strong>al</strong>, <strong>Liver</strong> <strong>and</strong> <strong>Nutritional</strong><br />
<strong>Problems</strong> <strong>in</strong> <strong>Fanconi</strong> <strong>Anemia</strong><br />
Sarah Jane Schwarzenberg, MD<br />
Pediatric Gastroenterology, Hepatology <strong>and</strong> Nutrition<br />
June 28, 2010
GI problems <strong>in</strong> FA<br />
• 7% have gastro<strong>in</strong>test<strong>in</strong>al tract abnormalities<br />
• GI symptoms common<br />
– Poor oral <strong>in</strong>take <strong>in</strong> some; overweight <strong>in</strong> others<br />
– Nausea<br />
– Abdom<strong>in</strong>al pa<strong>in</strong><br />
– Diarrhea<br />
• <strong>Liver</strong> adenomas associated with <strong>and</strong>rogen treatment<br />
• Complications of HSCT
Some conditions caus<strong>in</strong>g GI symptoms<br />
• Complications of anatomic gastro<strong>in</strong>test<strong>in</strong>al<br />
abnormalities<br />
– Strictures<br />
– Obstructions<br />
• Chronic <strong>in</strong>flammation/<strong>in</strong>fection<br />
– Diarrheal disease<br />
– Small bowel overgrowth<br />
• Medication side effects<br />
• Neurologic/behavioral problems
Gastroesophageal reflux<br />
• Commonly associated with esophageal<br />
atresia<br />
• Reflux may become more common with<br />
age<br />
• Medical management is essential to<br />
reduce complications<br />
• Many require anti-reflux surgery
Symptoms of GER<br />
• Heartburn<br />
• Abdom<strong>in</strong>al pa<strong>in</strong><br />
• Excessive burp<strong>in</strong>g, hiccup<strong>in</strong>g<br />
• Poor appetite, vomit<strong>in</strong>g<br />
• Poor sleep, nightmares
Small bowel overgrowth<br />
• Proliferation of bacteria <strong>in</strong> the small <strong>in</strong>test<strong>in</strong>e<br />
• Bacteria <strong>in</strong> small <strong>in</strong>test<strong>in</strong>e may be changed<br />
by antibiotic therapy<br />
• Associated with stasis<br />
– Impaired peristalsis<br />
– Abnormal anatomy<br />
– Bl<strong>in</strong>d loop
Symptoms of SBO<br />
• Excessive bowel gas<br />
• Diarrhea<br />
• Steatorrhea<br />
• Bloat<strong>in</strong>g<br />
• Abdom<strong>in</strong>al pa<strong>in</strong><br />
• <strong>Anemia</strong><br />
• B12 deficiency<br />
• Malabsorption<br />
• Weight loss/Failure to<br />
ga<strong>in</strong> weight
Rome II criteria<br />
• “Abdom<strong>in</strong>al pa<strong>in</strong> for at least 12 wk, which<br />
need not be consecutive, <strong>in</strong> the preced<strong>in</strong>g 12<br />
mo.”<br />
• Applies to:<br />
– Functional dyspepsia<br />
– Irritable bowel syndrome<br />
– Functional abdom<strong>in</strong>al pa<strong>in</strong><br />
– Abdom<strong>in</strong>al migra<strong>in</strong>e
Functional dyspepsia<br />
• Persistent or recurr<strong>in</strong>g upper abdom<strong>in</strong>al<br />
pa<strong>in</strong><br />
• No evidence of organic disease<br />
• No relief with defecation<br />
• No change <strong>in</strong> stool frequency or form
IBS<br />
• Abdom<strong>in</strong>al pa<strong>in</strong> characterized by 2 of the follow<strong>in</strong>g 3:<br />
– Relieved with defecation<br />
– Onset associated with change <strong>in</strong> stool frequency<br />
– Onset associated with change <strong>in</strong> stool form<br />
• No structural/metabolic cause<br />
• Supported by:<br />
– Abnormal stool frequency<br />
– Abnormal stool form<br />
– Abnormal stool passage<br />
– Mucus passed <strong>in</strong> stool<br />
– Bloat<strong>in</strong>g or feel<strong>in</strong>g of abdom<strong>in</strong>al distention
Functional abdom<strong>in</strong>al pa<strong>in</strong><br />
• Nearly cont<strong>in</strong>uous pa<strong>in</strong> <strong>in</strong> school age child<br />
• Rare relief of pa<strong>in</strong> with physiologic events<br />
• Some loss of daily function<strong>in</strong>g<br />
• Pa<strong>in</strong> that is not feigned<br />
• No evidence of other GI disorder to expla<strong>in</strong> pa<strong>in</strong>
Evaluation of gastro<strong>in</strong>test<strong>in</strong>al<br />
symptoms<br />
• Good history <strong>and</strong> physical exam<br />
• Blood for CRP, ESR, z<strong>in</strong>c level<br />
• Stool for ova <strong>and</strong> parasites, giardia, cryptosporidium<br />
• Ur<strong>in</strong>e culture<br />
• Hydrogen breath tests<br />
• Endoscopy with biopsy<br />
• Avoid radiographic imag<strong>in</strong>g, if possible
Alarm symptoms <strong>and</strong> signs<br />
• Involuntary weight loss<br />
• Deceleration of l<strong>in</strong>ear growth<br />
• <strong>Gastro<strong>in</strong>test<strong>in</strong>al</strong> blood loss<br />
• Significant vomit<strong>in</strong>g<br />
• Chronic severe diarrhea<br />
• Unexpla<strong>in</strong>ed fever<br />
• Persistent right upper or right lower quadrant pa<strong>in</strong><br />
• Family history of <strong>in</strong>flammatory bowel disease
Suggested treatment options<br />
• Acid suppression: Proton pump <strong>in</strong>hibitor<br />
• Gastric motility-promot<strong>in</strong>g agents<br />
– Erythromyc<strong>in</strong><br />
• Ant<strong>in</strong>ausea agents<br />
– Ondansetron (Zofran)<br />
• Treatment of small bowel overgrowth<br />
– Metronidazole (Flagyl)<br />
• Supplemental nutrition
Treatment of chronic abdom<strong>in</strong>al pa<strong>in</strong><br />
• Effective<br />
– Cognitive behavioral therapy for recurrent abdom<strong>in</strong>al pa<strong>in</strong><br />
– Famotid<strong>in</strong>e for dyspepsia<br />
– Pepperm<strong>in</strong>t oil for IBS<br />
• No evidence for benefit: Added dietary fiber, lactosefree<br />
diet, lactobacillus GG, analgesics,<br />
antispasmodics, sedatives, antidepressants
Poor growth <strong>in</strong> FA<br />
• Short stature associated with genetic<br />
defect: >50% have shorter than average<br />
height<br />
• Multiple endocr<strong>in</strong>e abnormalities<br />
• Inflammatory disease<br />
• Poor oral <strong>in</strong>take
Malnutrition<br />
• 22% children underweight for height<br />
• Measure height <strong>and</strong> weight at each visit<br />
• Failure to thrive<br />
– Weight for height persistently less than 85%<br />
– BMI persistently < 3 d percentile for age<br />
– Persistent decl<strong>in</strong>e <strong>in</strong> either measurement
Appetite stimulants<br />
• None tested directly <strong>in</strong> FA patients<br />
• Must evaluate first for treatable causes<br />
of poor <strong>in</strong>take<br />
• Weight ga<strong>in</strong>ed is usually lost when drug<br />
is stopped
Appetite Stimulants<br />
• Cyproheptad<strong>in</strong>e (Periact<strong>in</strong>)<br />
– M<strong>in</strong>imal weight ga<strong>in</strong><br />
– Well tolerated<br />
– Initial sleep<strong>in</strong>ess<br />
• Megestrol acetate (Megace)<br />
– M<strong>in</strong>imal weight ga<strong>in</strong><br />
– Adrenal <strong>in</strong>sufficiency, glucose <strong>in</strong>tolerance
Plan for supplemental feeds<br />
• <strong>Nutritional</strong> goals<br />
• Normal growth for genetic potential<br />
• Energy to meet dem<strong>and</strong>s of daily liv<strong>in</strong>g<br />
• Adequate reserve to face short-term malnourishment dur<strong>in</strong>g<br />
acute illness<br />
• Last<strong>in</strong>g benefits may require long-term therapy.<br />
• Supplementation through GI tract is preferable to<br />
supplementation by IV
Overweight<br />
• 27% FA patients overweight or obese<br />
• Associated with abnormal lipids<br />
• Associated with diabetes<br />
• Although failure to thrive has been a<br />
significant problem <strong>in</strong> FA, over-nutrition<br />
<strong>and</strong> metabolic syndrome are now be<strong>in</strong>g<br />
seen.<br />
Giri, et al. J Cl<strong>in</strong> Endocr<strong>in</strong>ol Metab 2007
Manag<strong>in</strong>g OW/OB<br />
• 6-day diet diary to <strong>in</strong>itiate dietary<br />
<strong>in</strong>tervention<br />
• Explore potential for exercise<br />
• Try to explore the family eat<strong>in</strong>g habits
5-2-1-0<br />
• “5 a day” fruits <strong>and</strong> vegetables<br />
• Less than 2 hr/day of screen time<br />
• At least 1 hour of moderate activity each day<br />
• No sweet dr<strong>in</strong>ks-0 pop, juice, Kool-ade, sports<br />
dr<strong>in</strong>ks, ect
GI conditions to consider<br />
before HSCT<br />
• Previous use of <strong>and</strong>rogens: US/CT/MRI<br />
liver<br />
• Chronic abdom<strong>in</strong>al pa<strong>in</strong>: consider<br />
endoscopy to detect potential bleed<strong>in</strong>g<br />
or <strong>in</strong>fectious risks<br />
• Chronic diarrhea: screen for <strong>in</strong>fections<br />
• Established liver disease
Long-term concerns after<br />
HSCT<br />
• <strong>Liver</strong><br />
– Chronic GVHD<br />
– Chronic viral hepatitis<br />
– Iron overload<br />
• Intest<strong>in</strong>e<br />
– Chronic GVHD with diarrhea <strong>and</strong> weight loss
<strong>Gastro<strong>in</strong>test<strong>in</strong>al</strong> graft-versushost<br />
disease<br />
• Complication of HSCT<br />
• Mild to very severe damage to l<strong>in</strong><strong>in</strong>g of<br />
GI tract<br />
• Severe, watery diarrhea <strong>and</strong>/or nausea<br />
<strong>and</strong> vomit<strong>in</strong>g<br />
• <strong>Liver</strong> may also be <strong>in</strong>volved with jaundice<br />
<strong>and</strong> reduced function
<strong>Gastro<strong>in</strong>test<strong>in</strong>al</strong> GVHD <strong>in</strong> FA<br />
• Incidence<br />
patients<br />
– Early data suggested <strong>in</strong>creased <strong>in</strong>cidence<br />
of GVHD <strong>in</strong> FA patients<br />
– Risk <strong>and</strong> severity have decreased as HCT<br />
has improved<br />
• May <strong>in</strong>crease risk of squamous cell<br />
carc<strong>in</strong>oma
Hepatic complications of<br />
<strong>and</strong>rogens<br />
• Hepatic adenoma 6-7%<br />
• Peliosis<br />
• Potential complications<br />
– Intrahepatic bleed<strong>in</strong>g<br />
– Hepatoma<br />
• Screen<strong>in</strong>g/Management
Screen<strong>in</strong>g for <strong>and</strong>rogenrelated<br />
liver disease<br />
• <strong>Liver</strong> enzymes every 3 months<br />
• Ultrasound every 6 months
Secondary iron overload<br />
• May lead to organ damage: liver, heart, pancreas<br />
• Screen<strong>in</strong>g<br />
– Serum iron<br />
– Transferr<strong>in</strong> saturation<br />
– Ferrit<strong>in</strong><br />
• Must confirm iron overload with liver biopsy or MRI
Vitam<strong>in</strong>s for cancer prevention<br />
• Speculation that FA is an oxidant stress disease<br />
• Diets high <strong>in</strong> vegetables <strong>and</strong> fruits may reduce the risk of<br />
some cancers<br />
• Individual vitam<strong>in</strong> preparations do not show similar results<br />
• Some vitam<strong>in</strong>s are toxic <strong>in</strong> excess<br />
• Vitam<strong>in</strong> A<br />
• Vitam<strong>in</strong> D<br />
• Vitam<strong>in</strong> C<br />
• Niac<strong>in</strong><br />
• Controlled cl<strong>in</strong>ical trials are essential to avoid unnecessary<br />
toxicity
Open<strong>in</strong>g March 2011<br />
• World-class care <strong>in</strong> more than<br />
50 pediatric specialties<br />
• All private patient rooms – 65%<br />
larger than national average<br />
• New Pediatric Emergency<br />
Department <strong>and</strong> Trauma<br />
Center<br />
• M<strong>in</strong>nesota’s first “green”<br />
children’s hospital