Gastroenterology and Feeding Issues in Fanconi Anemia
Gastroenterology and Feeding Issues in Fanconi Anemia
Gastroenterology and Feeding Issues in Fanconi Anemia
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<strong>Gastroenterology</strong> <strong>and</strong> <strong>Feed<strong>in</strong>g</strong><strong>Issues</strong> <strong>in</strong> <strong>Fanconi</strong> <strong>Anemia</strong>Sarah Jane Schwarzenberg, MDPediatric <strong>Gastroenterology</strong>, Hepatology <strong>and</strong> NutritionAugust 12, 2012
GI problems <strong>in</strong> FA• 5% have gastro<strong>in</strong>test<strong>in</strong>al tract abnormalities• Common gastro<strong>in</strong>test<strong>in</strong>al issues– Poor oral <strong>in</strong>take– Nausea– Abdom<strong>in</strong>al pa<strong>in</strong>– Diarrhea• Liver adenomas associated with <strong>and</strong>rogentreatment• Complications of stem cell transplant• Optimal nutrition <strong>in</strong> FA
Consider most significant problem• Abdom<strong>in</strong>al pa<strong>in</strong>?– Location– Incit<strong>in</strong>g agents• Nausea <strong>and</strong> vomit<strong>in</strong>g?– Time of day– Association with drugs or food• Excessive gas?A simple symptom diary for 1-3 monthsmay help with diagnosis
Some conditions caus<strong>in</strong>g GI symptoms• Complications of anatomic gastro<strong>in</strong>test<strong>in</strong>alabnormalities– Strictures– Obstructions• Chronic <strong>in</strong>flammation/<strong>in</strong>fection– Diarrheal disease– Small bowel overgrowth• Medication side effects• Neurologic/behavioral problems
Gastroesophageal reflux• Commonly associated with esophagealatresia• Reflux may become more common withage• Medical management is essential toreduce complications• Many require anti-reflux surgery
Symptoms of GER• Heartburn• Abdom<strong>in</strong>al pa<strong>in</strong>• Excessive burp<strong>in</strong>g, hiccup<strong>in</strong>g• Poor appetite, vomit<strong>in</strong>g• Poor sleep, nightmares
Small bowel overgrowth• Proliferation of bacteria <strong>in</strong> the small <strong>in</strong>test<strong>in</strong>e• Bacteria <strong>in</strong> small <strong>in</strong>test<strong>in</strong>e may be changedby antibiotic therapy• Risk <strong>in</strong>creased after previous gastro<strong>in</strong>test<strong>in</strong>alsurgery• Associated with stasis– Impaired peristalsis– Abnormal anatomy– Bl<strong>in</strong>d loop
Symptoms of SBO• Excessive bowel gas• Diarrhea• Steatorrhea• Bloat<strong>in</strong>g• Abdom<strong>in</strong>al pa<strong>in</strong>• <strong>Anemia</strong>• B12 deficiency• Malabsorption• Weight loss/Failure toga<strong>in</strong> weight
Evaluation of gastro<strong>in</strong>test<strong>in</strong>alsymptoms• Good history <strong>and</strong> physical exam• Diagnostic test<strong>in</strong>g possibilities based on history <strong>and</strong>physical exam– Blood for CRP, ESR– Stool for ova <strong>and</strong> parasites, giardia, cryptosporidium, otherpathogens– Ur<strong>in</strong>e culture– Hydrogen breath tests– Endoscopy with biopsy– Avoid radiographic imag<strong>in</strong>g, if possible• Ultrasound <strong>and</strong> MRI are safe
Alarm symptoms <strong>and</strong> signs• Involuntary weight loss• Deceleration of l<strong>in</strong>ear growth• Gastro<strong>in</strong>test<strong>in</strong>al blood loss• Significant vomit<strong>in</strong>g• Chronic severe diarrhea• Unexpla<strong>in</strong>ed fever• Persistent right upper or right lower quadrant pa<strong>in</strong>• Family history of <strong>in</strong>flammatory bowel disease
Suggested treatment options• Acid suppression: Proton pump <strong>in</strong>hibitor– Omeprazole, lansoprazole, etc.• Gastric motility-promot<strong>in</strong>g agents– Erythromyc<strong>in</strong>, Augment<strong>in</strong>• Ant<strong>in</strong>ausea agents– Ondansetron (Zofran)• Treatment of small bowel overgrowth– Metronidazole (Flagyl)• Supplemental nutrition
Non-specific management ofchronic abdom<strong>in</strong>al pa<strong>in</strong>• Evaluation completed <strong>and</strong> no clear etiology found• Thoughtful planned trials of therapy to reduce pa<strong>in</strong>,nausea or diarrhea can be done• Pa<strong>in</strong>– Acid suppression– Visual imag<strong>in</strong>g/self-hypnosis– Pepperm<strong>in</strong>t oil capsules– Trial rifaxim<strong>in</strong>• Nausea– Ondansetron– Visual imag<strong>in</strong>g/self-hypnosis• Diarrhea– Trial rifaxim<strong>in</strong>, nitazoxanide
Poor growth <strong>in</strong> FA• Short stature associated with geneticdefect: >50% have shorter than averageheight• >80% have endocr<strong>in</strong>e abnormalities• Inflammatory disease/elevated TNF• Poor oral <strong>in</strong>take
Malnutrition• 22% children underweight for height• Measure height <strong>and</strong> weight at each visit• Failure to thrive– Weight for height persistently less than 85%– BMI persistently < 3 d percentile for age– Persistent decl<strong>in</strong>e <strong>in</strong> either measurement
Appetite stimulants• None tested directly <strong>in</strong> FA patients• Must evaluate first for treatable causesof poor <strong>in</strong>take• Weight ga<strong>in</strong>ed is usually lost when drugis stopped
Appetite Stimulants• Cyproheptad<strong>in</strong>e (Periact<strong>in</strong>)– M<strong>in</strong>imal weight ga<strong>in</strong>– Well tolerated– Initial sleep<strong>in</strong>ess• Megestrol acetate (Megace)– M<strong>in</strong>imal weight ga<strong>in</strong>– Adrenal <strong>in</strong>sufficiency, glucose <strong>in</strong>tolerance
Plan for supplemental feeds• Nutritional goals• Normal growth for genetic potential• Energy to meet dem<strong>and</strong>s of daily liv<strong>in</strong>g• Adequate reserve to face short-term malnourishment dur<strong>in</strong>gacute illness• Last<strong>in</strong>g benefits may require long-term therapy.• Supplementation through GI tract is preferable tosupplementation by IV
Overweight• 27% FA patients overweight or obese• Associated with abnormal lipids• Associated with diabetes• Although failure to thrive has been asignificant problem <strong>in</strong> FA, over-nutrition<strong>and</strong> metabolic syndrome are now be<strong>in</strong>gseen.Giri, et al. J Cl<strong>in</strong> Endocr<strong>in</strong>ol Metab 2007
Manag<strong>in</strong>g OW/OB• 6-day diet diary to <strong>in</strong>itiate dietary<strong>in</strong>tervention• Explore potential for exercise• Try to explore the family eat<strong>in</strong>g habits
5-2-1-0• “5 a day” fruits <strong>and</strong> vegetables• Less than 2 hr/day of screen time• At least 1 hour of moderate activity each day• No sweet dr<strong>in</strong>ks-0 pop, juice, Kool-ade, sportsdr<strong>in</strong>ks, ect
GI evaluation at the time ofstem cell transplant• Previous use of <strong>and</strong>rogens: US/CT/MRIliver• Chronic abdom<strong>in</strong>al pa<strong>in</strong>: considerendoscopy to detect potential bleed<strong>in</strong>gor <strong>in</strong>fectious risks• Chronic diarrhea: screen for <strong>in</strong>fections• Established liver disease• Nutritional status
GI concerns after stem celltransplant• Liver– Chronic graft versus host disease– Chronic viral hepatitis– Iron overload• Intest<strong>in</strong>e– Chronic graft versus host disease with diarrhea<strong>and</strong> weight loss
Gastro<strong>in</strong>test<strong>in</strong>al graft-versushostdisease• Complication of stem cell transplant• Mild to very severe damage to l<strong>in</strong><strong>in</strong>g ofGI tract• Severe, watery diarrhea <strong>and</strong>/or nausea<strong>and</strong> vomit<strong>in</strong>g• Liver may also be <strong>in</strong>volved with jaundice<strong>and</strong> reduced function
Gastro<strong>in</strong>test<strong>in</strong>al GVHD <strong>in</strong> FA• Incidencepatients– Early data suggested <strong>in</strong>creased <strong>in</strong>cidenceof GVHD <strong>in</strong> FA patients– Risk <strong>and</strong> severity have decreased as HCThas improved• May <strong>in</strong>crease risk of squamous cellcarc<strong>in</strong>oma
Hepatic complications of<strong>and</strong>rogens• Hepatic adenoma 6-7%• Peliosis• Potential complications– Intrahepatic bleed<strong>in</strong>g– Hepatoma• Screen<strong>in</strong>g/Management
Screen<strong>in</strong>g for <strong>and</strong>rogenrelatedliver disease• Liver enzymes every 3 months• Ultrasound every 6 months• Consider resection if size <strong>in</strong>creas<strong>in</strong>g
Secondary iron overload• May lead to organ damage: liver, heart, pancreas• Screen<strong>in</strong>g– Serum iron– Transferr<strong>in</strong> saturation– Ferrit<strong>in</strong>• Must confirm iron overload with liver biopsy orspecialized MRI
Micronutrient supplementation<strong>in</strong> FA• Many <strong>in</strong>dividuals <strong>and</strong> families supplement vitam<strong>in</strong>s,flavonoids, <strong>and</strong> other micronutrients• Supplements are proposed to alter the oxidative stress <strong>and</strong><strong>in</strong>creased <strong>in</strong>flammatory reaction found <strong>in</strong> FA• While we depend on oxygen for life, oxygen is a deadlypoison• All terrestrial life controls oxygen toxicity through reactionscalled Red-Ox (reduction-oxidation reactions)• Some evidence suggests that the FA participates <strong>in</strong>regulat<strong>in</strong>g oxidative stress• Patients with FA also have <strong>in</strong>creased production of<strong>in</strong>flammatory cytok<strong>in</strong>es
Supplements <strong>in</strong> FA• Biology of FA suggests reduc<strong>in</strong>goxidative stress might reduce cancer• Unclear if supplements can be safelydelivered at level to make a difference• R<strong>and</strong>omized cl<strong>in</strong>ical trials are difficult <strong>in</strong>a highly variable, rare disease• Information from other diseases may beof value.
Micronutrient supplementation<strong>and</strong> cancer prevention• Trials target<strong>in</strong>g populations with nutrientdeficiency may prevent cancer• Supplementation <strong>in</strong> populations withhigher nutritional status or to achievepharmacological exposures maypromote cancer
Effects of anti-oxidant supplements• 78 trials, 296,707 participants <strong>in</strong>r<strong>and</strong>omized trials of anti-oxidants versusplacebo• Anti-oxidants do not decrease mortality• Some anti-oxidants appear to <strong>in</strong>creasemortality– Vitam<strong>in</strong> A, vitam<strong>in</strong> E-carotene• No evidence of problems with Vitam<strong>in</strong> C<strong>and</strong> selenium
Fruits <strong>and</strong> Vegetables vs. Supplements• Fruits, vegetables, tea <strong>and</strong> cocoa arerich natural sources of flavonoids• High <strong>in</strong>take of these foods decrease riskof cardiovascular disease; supplementslack the same evidence• Micronutrients from fruits <strong>and</strong>vegetables are not reproduced <strong>in</strong>supplements
Suggested guidel<strong>in</strong>es• Diet should be high <strong>in</strong> highly colorfulfruits <strong>and</strong> vegetables (5 or moreserv<strong>in</strong>gs each day)• Flavonoid supplements or <strong>in</strong>dividualvitam<strong>in</strong>s should be viewed as drugs– Have side-effects– Interact with other medications <strong>and</strong>nutrients– May alter absorption of other nutrients