1 CPC Madhurima Gupta, MD John F Pohl, MD 29 th Sep 2004.

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CPC

Madhurima Gupta, MDJohn F Pohl, MD29th Sep 2004

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A 5-year old male with intermittent vomiting, abdominal pain and CNS changes seen on head MRI…

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CC

Intermittent vomiting for 2 years

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HOPI Vomiting

Non-bloody, non-bilious Progresses to multiple emesis episodes leading to

dehydration Associated with abdominal pain (diffuse in nature) Recurrent pattern

≥ 12 hours of sleep after vomiting episodes Two of these episodes led to hospitalization at an

outside institution in the past two years No associated diarrhea, constipation, hematochezia,

melena, dysphagia, fever, headache, dysuria, weight loss or rashes.

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PMHx Term, vaginal delivery without

complications. Pneumonia X 2 Chronic otitis media and allergic

rhinitis Previous Giardia infection 2 previous hospital admissions

for dehydration

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History

Past surgical history Bilateral tympanostomy tube placement & Adenoidectomy

Medications: None Drug Allergies: None

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Family History 7-year old brother with a history of

insulin-dependent diabetes mellitus, constipation, H/O Giardia infection and “wheat allergy”

Mother has irritable bowel syndrome

Father has “stomach problems” Paternal grandmother has “wheat

allergy”

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Social History

Attends kindergarten No significant psychosocial

stressors No recent travel No tobacco exposure.

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Physical Exam VS: T 36o C, Pulse 97, R 12, BP 96/51, Wt.

19.5 kg(75%), Ht. 109 cm(50%) Gen: Alert, talkative, no distress noted. HEENT: Sclerae non-icteric. Nares

patent and clear. Oropharynx clear. Tympanic membranes normal. Neck has normal ROM.

Lymph nodes: No adenopathy noted. Heart: NSR without appreciable murmur Lungs: Clear

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Physical Exam: Cont… Abdomen: Soft. Bowel sounds

normal. No HSM. No palpable masses. No tenderness.

Genitalia: Tanner I male, circumcised, testes descended bilaterally.

Rectal: Normal Skin: No rashes. Neuro: No focal neurological deficits

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Labs

T. Prot N6.9 (6-8)

Alb 4.7 (4-6)

ALT 20 (0-35)

AST 35 (0-35)

T. Bili 0.8 (0.1-1.0)

D. Bili 0.3 (0-0.4)

Alk. P 255 (to-345)

Amylase N39 (<120)

Lipase 98 (0-160)

Ammonia 11 (29-70)

Lactic acid 1.5 (0.2-0.8)

Pyruvate 0.08 (0.7-0.12)

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Labs: Cont…

6.9WBC

12.5 Hbg

36.8 Hct341,000Platelets

G78 L13 M8

0.3 Cr16 CO24.6 K

17 BUN98 Cl137 Na

65 BS

AG = 23

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Labs: Cont… Serum amino acid screen: Normal Urine organic acid screen: Increased

3-hydroxybutyric & acetoacetic acid UA

Sp. gravity 1.032 pH 5.5 4+ ketones Negative blood, glucose, protein, nitrite,

leukocyte esterase, bilirubin RBCs, WBCs, Bacteria: 0

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Radiographic studies Upper GI barium series: Normal

Head MRI: Scattered areas of increased signal intensity particularly noted in the subcortical white matter regions. These areas are read as possibly post-ischemic, post-inflammatory or demyelinating lesions.

15MRI of the Brain

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Pertinent points Recurrent vomiting episodes associated with

abdominal pain Family H/O “wheat allergy” in older brother &

paternal grandmother Labs:

Metabolic acidosis Increased 3-hydroxybutyric and acetoacetic acid

on urinary organic acid screen 4+ ketones on UA

Head MRI: Scattered areas of increased signal intensity particularly in the subcortical white matter regions.

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Differential diagnosis

Lead poisoning Reye syndrome Inborn errors of metabolism Brain tumor GI obstruction Celiac Disease Cyclic vomiting syndrome-Secondary

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Lead poisoning Most common metal poisoning

Due to widespread presence of lead containing products in industrial and residential settings

Interferes with biosynthesis of heme Disturbs calcium metabolism BLL

Gold standard for determining health effects (ideal value=0)

CDC & AAP consider up to 10μg/dL acceptable

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Clinical presentation Acute intoxication (BLL>80 μg/dL)

Crampy abdominal pain with or without neurologic or constitutional complaints ranging from headache and malaise to overt encephalopathy

Chronic lead toxicity More common Characterized by multisystemic signs

and symptoms

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Clinical presentation: Cont… Gastrointestinal symptoms

Anorexia, abdominal pain, vomiting and constipation

Occurring and recurring over a period of weeks.

Associated CNS and behavioral symptoms Lead encephalopathy has been

associated with softening and flattening of convolutions in the brain

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Differential diagnosis

× Lead poisoning Reye syndrome Inborn error of metabolism Brain tumor GI obstruction Celiac Disease Cyclic vomiting syndrome-

Secondary

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Reye Syndrome Definition: Acute, noninflammatory

encephalopathy with altered levels of consciousness and liver dysfunction

May be a multiorgan disease due to diffuse mitochondrial injury of unknown origin

No toxic factor identified yet Studies suggest etiologic link b/w the use

of aspirin & viral infections (varicella & Influenza B)

Avoid the use of aspirin as an antipyretic in pediatric patients with influenza or varicella.

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Clinical presentation Classic case: Stereotypic, biphasic course

Prodromal febrile illness (URI or chickenpox) Followed by an interval in which the child has

seemingly recovered Abrupt onset of protracted vomiting (usually

within 5–7 days after the onset of the viral illness)

Delirium, combative behavior and stupor may follow within a few hours after onset of vomiting

Neurologic symptoms may rapidly progress to seizures, coma and death

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Diagnosis AST & ALT: Can be be up to 30

times normal values Ammonia: Thrice the normal range

or more Increased Lactic acid & organic

acids CT or MRI: “Normal brain” or

“diffuse cerebral edema with ventricular compression”

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Differential diagnosis

× Lead poisoning × Reye syndrome Inborn error of metabolism Brain tumor GI obstruction Celiac Disease Cyclic vomiting syndrome-

Secondary

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Inborn Errors of Metabolism

IEMs associated with metabolic acidosis Organic acidemias (methylmalonic,

propionic, isovaleric acidemia) Defects in pyruvate metabolism Defects in the respiratory chain:

Primary lactic acidosis

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IEMs: Cont… Symptoms of late onset IEMs (partial

defect) Vomiting, respiratory distress and changes in

mental status Symptoms usually brought on by process

causing increased catabolism like intercurrent illness

Initial tests to r/o IEMs CBC, Chem-7, AST/ALT, T. & D. Bilirubin, plasma

ammonia/lactate/pyruvate/amino acids and urine dipstick/organic acids

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Differential diagnosis

× Lead poisoning

× Reye syndrome

× Inborn error of metabolism Brain tumor GI obstruction Celiac Disease Cyclic vomiting syndrome-Secondary

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Brain tumor Primary tumors of brain

Second most common cancer in children (after leukemia)

Most common solid tumor Two thirds of all intracranial tumors in children

b/w ages of 2 and 12 yr are infratentorial Most common infratentorial tumors in children:

Cerebellar astrocytoma, medulloblastoma, brain stem gliomas, ependymoma

Most common supratentorial tumors: Craniopharyngioma, optic nerve gliomas, choroid plexus papilloma

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Clinical presentation Clinical Presentation varies

Depending on the location, type, rate of growth of the tumor and the age of the child.

Two distinct patterns of presentation Infratentorial: Symptoms and signs of increased

intracranial pressure (ICP) Supratentorial: Focal neurologic signs & seizures

Alterations in personality are often the first symptom

Child may become lethargic, irritable, hyperactive, forgetful or may perform poorly academically

MRI is the neuroimaging standard for primary brain tumors

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Differential diagnosis

× Lead poisoning × Reye syndrome × Inborn error of metabolism × Brain tumor GI obstruction Celiac Disease Cyclic vomiting syndrome-Secondary

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GI obstruction Most common cause of nonbilious vomiting

is gastric outlet obstruction Caused by pyloric atresia, antral webs, gastric

duplications and gastric volvulus Other symptoms

Nausea, abdominal distension and abdominal pain

Abdominal plain radiographs: Dilated stomach

Upper gastrointestinal contrast series is usually diagnostic

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Differential diagnosis

× Lead poisoning × Reye syndrome × Inborn error of metabolism × Brain tumor × GI obstruction Celiac Disease Cyclic vomiting syndrome-Secondary

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Celiac disease Autoimmune inflammatory disease of the

small intestine that is precipitated by the ingestion of gluten (component of wheat protein) in genetically susceptible persons

Intra familial occurrences happen frequently

Disorder develops after dietary exposure to protein gluten (found in wheat, rye and barley)

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Celiac Disease: Cont… Immunologic response involves activation

of inflammatory response by CD4+ gluten-sensitive T cells resulting in villus atrophy, crypt hyperplasia and damage to the surface epithelium in the small bowel

The injury is greatest in the proximal small bowel which explains the variable degree of malabsorption

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Clinical presentation

May present at any age after introduction of gluten to diet

Nonintestinal features are equally as common as GI symptoms

Commonly manifests as “silent” celiac disease (i.e. minimal or no symptoms)

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Clinical Presentation: Cont…

Older children may present with abdominal pain, vomiting, anorexia, diarrhea, arthritis/arthralgia, anemia

Extraintestinal symptoms & signs result from nutrient malabsorption & may involve virtually all organ systems

Extraintestinal manifestations may include demyelinating CNS lesions

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Diagnosis Serologic testing should be considered in

patients with increased genetic risk and in patients who have chronic diarrhea, recurrent vomiting, unexplained anemia, chronic fatigue or unexplained weight loss.

Current serum immunologic markers have increased sensitivity and specificity for diagnosis: IgA endomysial, tissue transglutaminase & anti-gliadin antibodies

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Diagnosis: Cont… Clinical symptoms and serologic

markers may suggest diagnosis but histologic confirmation is mandatory

Characteristic include villus atrophy, crypt hyperplasia and infiltration of the lamina propria with chronic inflammatory cells

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Differential diagnosis

× Lead poisoning × Reye syndrome × Inborn error of metabolism × Brain tumor × GI obstruction Celiac Disease Cyclic vomiting syndrome-Secondary

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Cyclic vomiting syndrome Syndrome with numerous episodes of vomiting

(about nine episodes/mo) interspersed with well intervals

Onset - 3 to 5 yr of age Episodes last 2–3 days, with four or more

emesis episodes per hour Idiopathic cyclic vomiting may be a migraine

equivalent (abdominal migraine) Radiographic studies of GI tract & neurologic

evaluation (CT or MRI) rule out most organic lesions that may produce recurrent vomiting

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Differential diagnosis

× Lead poisoning × Reye syndrome × Inborn error of metabolism × Brain tumor × GI obstruction Celiac Disease Cyclic vomiting syndrome-Secondary

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Final Diagnosis:

Celiac Disease Cyclic vomiting syndrome -

secondary

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Further testing

IgA endomysial antibodies IgA tissue transglutaminase

antibodies IgA anti-gliadin antibodies Small intestinal endoscopic biopsy

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The End

Proceed to post test Download post test Complete post test Return post test to Dr. Sandra

Oliver

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Post test question 1

1. Increased ketones in the urine may occur in all the folllowing except:

A.Renal GlycosuriaB.StarvationC.Metabolic AlkalosisD.Hyperthyroidism

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Post test question 2

2. Which incorrectly describes Lead Poisoning

A. Stimulates heme and globin synthesis

B. Disturbs calcium metabolismC. Results in abdominal discomfortD. Causes irreversible mental

retardation

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Post test question 3

1. IEMs are associated with which of the following exceptA. Hypoammonemia B. Metabolic AcidosisC. Hyperglycemia D. Metabolic encephalopathy

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Post test question 4

4. Celiac disease is correctly described by which of the following:

A. Autoimmune inflammatory disease of the large intestine

B. Replacement of long villi and short crypts with short or absent villi and hyperplastic crypts.

C. Inappropriate B-cell response to glutenD. Immunoglobulin (Ig)A antibodies are

present in perimysium