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Clinical Challenges and Images in GI
Clinical Challenges and Images in GI continued
Image 2
Question: A 31-week-old male born at another hospital due to premature rupture of membranes developed metabolic acidosis when he was 3 days old; bicarbonate was 14 mmol/L and pH, 7.25. The patient received sodium bicarbonate daily, and acetate was maximized in his total parental nutrition (TPN) for 5 days. Metabolic workup revealed normal lactic acid, ammonia, and multiple elevations in the amino acid profile secondary to TPN. On day 12, records indicate that the patient’s condition deteriorated, and he was transferred for metabolic acidosis, renal disorder, and hepatic disorder. At the time of transfer, the patient had 1 acholic stool, elevated creatinine of 2.6 mg/dL, and blood urea nitrogen (BUN) of 72 mg/dL, elevated potassium of 7.2 mmol/L, low bicarbonate of 11 mmol/L, and a direct bilirubin of 5 mg/dL. Upon transfer to our facility, the patient’s heart rate was 180 bpm, blood pressure 57/32, and weight 1469 g (birth weight, 1740 g). Physical examination revealed a lethargic and moderately dehydrated infant. Laboratory values were: potassium 5.8 mmol/L, bicarbonate 12 mmol/L, BUN 75 mmol/L, creatinine 3.2 mmol/L, total bilirubin 5.8 mg/dL with a direct of 4.7 mg/dL, and normal liver transaminases. His course in the neonatal intensive care unit was marked by renal insufficiency, metabolic acidosis, dehydration, direct hyperbilirubinemia, and periods of anuria secondary to severe dehy-
dration. Infectious, metabolic, and renal causes were ruled out as etiologies, and the suspected cause of the metabolic acidosis was the patient’s protracted diarrhea. An evaluation for congenital diarrhea was done that included stool electrolytes and an upper endoscopy and sigmoidoscopy. Stool electrolytes revealed abnormally high levels of potassium (4.7), sodium (139), chloride (105), and osmolarity (279 mOs/kg). Also, his stool output was 100 mL/kg per day. Figure 1A shows the patient’s duodenal biopsy. What is your diagnosis? Look on page 1639 for the answer and see the GASTROENTEROLOGY website (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. MELINDA O. AMOSU, MD HAYAT M. MOUSA, MD Columbus Children’s Hospital and Ohio State University MARK LUQUETTE, MD Columbus Children’s Hospital Columbus, Ohio
© 2007 by the AGA Institute
0016-5085/07/$32.00 doi:10.1053/j.gastro.2007.02.062
1225
April 2007
CLINICAL CHALLENGES AND IMAGES IN GI
1639
Answer to the Clinical Challenges and Images in GI Question: Image 2 (page 1225): Microvillous Inclusion Disease Study of the periodic Acid-Schiff (PAS) stain of the duodenal biopsy showed marked attenuation of the brush border and numerous PAS positive, diastase resistant inclusions in the apical cytoplasm of surface epithelium. A high magnification of the surface epithelium (B) shows a linear staining of the luminal aspect of the epithelium marking the brush border (arrow). Panels C and D, respectively, show the brush border (arrows) staining with immunostains for CD10 and CEA. Ultrastructural studies showed findings diagnostic of microvillous inclusion disease (MID) and include attenuated microvilli (E) and classic inclusions (F, arrows). MID is among several causes of protracted diarrhea in infancy. Some others include congenital lactose deficiency, congenital chloride diarrhea, congenital sodium diarrhea, and tufting enteropathy. Of these disorders, MID appears to be the most common.1 It is inherited in an autosomal-recessive manner.2 Possible etiologies are defective protein trafficking and abnormal cytoskeletal and microfilament functioning.3 For MID there is a blockage in the transport pathway from the Golgi, which leads to fusion of the small vesicles into vesicular bodies. These vesicular bodies then form inclusions or larger vesicles that line the microvilli.4 Diarrhea in MID is frequently profuse and watery. An infant with MID can have up to 100 –500 mL/kg per day of stool output.5 The diarrhea usually begins within the first 72 hours of life with rapid progression to severe dehydration. On TPN the diarrhea continues, but becomes less voluminous.5 Diagnosis is best made by intestinal biopsy. Electron microscopy shows intracytoplasmic microvillus inclusions in the surface epithelial cells, which is diagnostic.2 On light microscopy, severe diffuse villous atrophy is seen, with or without crypt hypoplasia and no increased cellularity of the lamina propria. With PAS stain and immunohistochemistry the disruption in the brush border and intracytoplasmic inclusions can be seen.3,6 Once diagnosis is confirmed, the only treatment is small bowel transplant. This patient is stable at home and is currently on the list for a small bowel and liver transplant. References 1. Garcia-Careaga M, Kerner J. Malabsorptive disorders. In: Behrman RE, Kliegman RM. Jenson HB. Nelson textbook of pediatrics, 17th ed. Philadelphia: Saunders, 2004. 2. Sherman P, Mitchel D, Cutz E. Neonatal enteropathies: defining the causes of protracted diarrhea of infancy. J Pediatr Gastroenterol Nutr 2004;38:16 –26. 3. Rund C, Carmichael B, Harris A, Schaffner V. Small bowel biopsy in a 6-week-old infant. Arch Pathol Lab Med 2006;130:e19 – e21. 4. Mierau G, Wills EJ, Wyatt-Ashmead J, Hoffenberg E, Cutz E. Microvillous inclusion disease: report of a case with atypical features. Ultrastructural Pathol 2001;25:517–521. 5. Kueˇinskiene˙ R, Janeˇiauskas D, Pužas A, Adamonis K. Microvillous inclusion disease. Medicina (Kaunas) 2004;40:864 – 867. 6. Groisman GM, Amar M, Livne E. CD10: a valuable tool for the light microscopic diagnosis of microvillous inclusion disease (familial microvillous atrophy). Am J Surg Pathol 2002;26:902–907.
For submission instructions, please see the GASTROENTEROLOGY website (www.gastrojournal.org).
Image 2
Question: A 31-week-old male born at another hospital due to premature rupture of membranes developed metabolic acidosis when he was 3 days old; bicarbonate was 14 mmol/L and pH, 7.25. The patient received sodium bicarbonate daily, and acetate was maximized in his total parental nutrition (TPN) for 5 days. Metabolic workup revealed normal lactic acid, ammonia, and multiple elevations in the amino acid profile secondary to TPN. On day 12, records indicate that the patient’s condition deteriorated, and he was transferred for metabolic acidosis, renal disorder, and hepatic disorder. At the time of transfer, the patient had 1 acholic stool, elevated creatinine of 2.6 mg/dL, and blood urea nitrogen (BUN) of 72 mg/dL, elevated potassium of 7.2 mmol/L, low bicarbonate of 11 mmol/L, and a direct bilirubin of 5 mg/dL. Upon transfer to our facility, the patient’s heart rate was 180 bpm, blood pressure 57/32, and weight 1469 g (birth weight, 1740 g). Physical examination revealed a lethargic and moderately dehydrated infant. Laboratory values were: potassium 5.8 mmol/L, bicarbonate 12 mmol/L, BUN 75 mmol/L, creatinine 3.2 mmol/L, total bilirubin 5.8 mg/dL with a direct of 4.7 mg/dL, and normal liver transaminases. His course in the neonatal intensive care unit was marked by renal insufficiency, metabolic acidosis, dehydration, direct hyperbilirubinemia, and periods of anuria secondary to severe dehy-
dration. Infectious, metabolic, and renal causes were ruled out as etiologies, and the suspected cause of the metabolic acidosis was the patient’s protracted diarrhea. An evaluation for congenital diarrhea was done that included stool electrolytes and an upper endoscopy and sigmoidoscopy. Stool electrolytes revealed abnormally high levels of potassium (4.7), sodium (139), chloride (105), and osmolarity (279 mOs/kg). Also, his stool output was 100 mL/kg per day. Figure 1A shows the patient’s duodenal biopsy. What is your diagnosis? Look on page 1639 for the answer and see the GASTROENTEROLOGY website (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. MELINDA O. AMOSU, MD HAYAT M. MOUSA, MD Columbus Children’s Hospital and Ohio State University MARK LUQUETTE, MD Columbus Children’s Hospital Columbus, Ohio
© 2007 by the AGA Institute
0016-5085/07/$32.00 doi:10.1053/j.gastro.2007.02.062
1225
April 2007
CLINICAL CHALLENGES AND IMAGES IN GI
1639
Answer to the Clinical Challenges and Images in GI Question: Image 2 (page 1225): Microvillous Inclusion Disease Study of the periodic Acid-Schiff (PAS) stain of the duodenal biopsy showed marked attenuation of the brush border and numerous PAS positive, diastase resistant inclusions in the apical cytoplasm of surface epithelium. A high magnification of the surface epithelium (B) shows a linear staining of the luminal aspect of the epithelium marking the brush border (arrow). Panels C and D, respectively, show the brush border (arrows) staining with immunostains for CD10 and CEA. Ultrastructural studies showed findings diagnostic of microvillous inclusion disease (MID) and include attenuated microvilli (E) and classic inclusions (F, arrows). MID is among several causes of protracted diarrhea in infancy. Some others include congenital lactose deficiency, congenital chloride diarrhea, congenital sodium diarrhea, and tufting enteropathy. Of these disorders, MID appears to be the most common.1 It is inherited in an autosomal-recessive manner.2 Possible etiologies are defective protein trafficking and abnormal cytoskeletal and microfilament functioning.3 For MID there is a blockage in the transport pathway from the Golgi, which leads to fusion of the small vesicles into vesicular bodies. These vesicular bodies then form inclusions or larger vesicles that line the microvilli.4 Diarrhea in MID is frequently profuse and watery. An infant with MID can have up to 100 –500 mL/kg per day of stool output.5 The diarrhea usually begins within the first 72 hours of life with rapid progression to severe dehydration. On TPN the diarrhea continues, but becomes less voluminous.5 Diagnosis is best made by intestinal biopsy. Electron microscopy shows intracytoplasmic microvillus inclusions in the surface epithelial cells, which is diagnostic.2 On light microscopy, severe diffuse villous atrophy is seen, with or without crypt hypoplasia and no increased cellularity of the lamina propria. With PAS stain and immunohistochemistry the disruption in the brush border and intracytoplasmic inclusions can be seen.3,6 Once diagnosis is confirmed, the only treatment is small bowel transplant. This patient is stable at home and is currently on the list for a small bowel and liver transplant. References 1. Garcia-Careaga M, Kerner J. Malabsorptive disorders. In: Behrman RE, Kliegman RM. Jenson HB. Nelson textbook of pediatrics, 17th ed. Philadelphia: Saunders, 2004. 2. Sherman P, Mitchel D, Cutz E. Neonatal enteropathies: defining the causes of protracted diarrhea of infancy. J Pediatr Gastroenterol Nutr 2004;38:16 –26. 3. Rund C, Carmichael B, Harris A, Schaffner V. Small bowel biopsy in a 6-week-old infant. Arch Pathol Lab Med 2006;130:e19 – e21. 4. Mierau G, Wills EJ, Wyatt-Ashmead J, Hoffenberg E, Cutz E. Microvillous inclusion disease: report of a case with atypical features. Ultrastructural Pathol 2001;25:517–521. 5. Kueˇinskiene˙ R, Janeˇiauskas D, Pužas A, Adamonis K. Microvillous inclusion disease. Medicina (Kaunas) 2004;40:864 – 867. 6. Groisman GM, Amar M, Livne E. CD10: a valuable tool for the light microscopic diagnosis of microvillous inclusion disease (familial microvillous atrophy). Am J Surg Pathol 2002;26:902–907.
For submission instructions, please see the GASTROENTEROLOGY website (www.gastrojournal.org).