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Lysinuric protein intolerance masquerading as celiac disease: A case report
L
Lysinuric protein intolerance masquerading as celiac disease: A case report
Manuel A. Reinoso, MD, Chester Whitley, MD, Jose Jessurun, MD, and Sarah Jane Schwarzenberg, MD
A 5 1/2-year-old boy presented with delayed growth, chronic diarrhea, and hypoproteinemia. Clinical presentation, initial laboratory data, and evaluation of an intestinal biopsy specimen suggested a diagnosis of celiac disease. Symptoms did not resolve on a gluten-free diet. The development of hyperammonemia prompted further studies that led to the diagnosis of lysinuric protein intolerance. Lysinuric protein intolerance, although a rare disorder, should be included in the differential diagnosis of conditions associated with intestinal villous atrophy. ( J Pediatr 1998;132:153-5)
Lysinuric protein intolerance is a rare autosomal recessive disorder in which there is increased urinary excretion and clearance of all cationic amino acids, especially of lysine. Cationic amino acids are also poorly absorbed from the intestine. Patients are usually asymptomatic in infancy, especially when breast-fed, but after weaning symptoms of poor appetite, diarrhea, poor growth, and irritability develop. If untreated, hepatosplenomegaly develops, as well as muscle hypotonia, sparse hair, and osteoporosis. Mental development varies from normal to moderate delay.1 We report a patient with LPI whose clinical presentation and histologic findings on a duodenal biopsy specimen suggested an initial diagnosis of celiac sprue.
CASE
REPORT
A 5 1/2-year-old white boy was seen at the University of Minnesota with complaints of abdominal pain, diarrhea, vomiting, poor appetite, and fatigue for more
than 2 months. The child was reportedly small in stature since early childhood. He had refused meat and dairy products since early life, preferentially eating cereals, vegetables, and yogurt. The rest of his family were meat eaters. An older sibling was growing normally and there were no other family members with similar symptomatology. His parents denied consanguinity. The physical examination was remarkable for pallor, thin and light-colored hair, and pitting edema of lower extremities. His weight of 14.7 kg and height of 98 cm were both below the 5th percentile for his age. There was dry, scaly skin on his ankles and feet and sores in the corners of his mouth. No visceromegaly was detected by examination. Laboratory data were as follows: serum sodium, 132 mmol/L (132 mEq/L); serum total CO2, 24 mmol/L; serum albumin, 17 gm/L (1.7 gm/dl); hemoglobin, 1.4 mmol/ L (9 gm/dl); platelet count, 170 × 109/L (170,000/mm3); prothrombin time, 12.8 sec; serum zinc, 6 mmol/L (39 mg/dl);
From the Department of Pediatrics, Division of Pediatric Gastroenterology and Nutrition, Division of Genetics and Metabolism; the Institute of Human Genetics and Department of Pathology and Laboratory Medicine; University of Minnesota, Minneapolis. Submitted for publication Mar. 18, 1996; accepted Feb. 12, 1997. Reprint requests: Sarah J. Schwarzenberg, MD, Box 185 UMHC, Minneapolis, MN 55455. Copyright © 1998 by Mosby, Inc. 0022-3476/98/$5.00 + 0 9/22/81203
serum iron, 2.3 mmol/L (13 mg/dl); transferrin, 60 mg/dl. Antiendomysium IgA and antigliadin IgA and IgG antibody tests were negative. Total IgA was not measured. Spot stool samples were positive for fecal fat. Urinalysis, thyroid studies, renal function, and aminotransferases were normal. Bone age was delayed more than 2 standard deviations and osteopenia was noted. He was anergic to the tuberculin, Candida, and tetanus skin tests. LPI
Lysinuric protein intolerance
Esophagogastroduodenoscopy with small intestinal biopsy was performed. Histopathologic examination of the fourth portion of the duodenal mucosa showed blunting of villi with elongation of crypts. The surface epithelium showed numerous intraepithelial lymphocytes and shortening of cells. The lamina propria was mildly expanded by plasma cells and lymphocytes (Figure). These changes were interpreted as consistent with celiac disease. The child was started on a gluten-free diet and was discharged home on vitamin K, iron, and zinc replacement therapy. One month later his diarrhea and emesis persisted and he had lost weight. He was admitted and started on nasogastric tube feedings with a complete pediatric liquid formula, Pediasure (Ross Products Division, Abbott Laboratories, Columbus, Ohio). He received 1.9 gm protein/kg per day. Albumin infusions were given, followed by diuretics, to reduce edema. Prednisone at 1 mg/kg per day was started to diminish inflammation. After 24 hours of enteral nutrition, the patient became increasingly irritable, but his level of consciousness was always preserved. An increased ammonia level of 78 153
REINOSO
ET AL.
THE JOURNAL
Figure. The duodenal biopsy specimen showed marked blunting of the villi, elongation of crypts (left), increased number of plasma cells and lymphocytes in the lamina propria, and many intraepithelial lymphocytes (right). This biopsy specimen was reviewed retrospectively after the diagnosis of lysinuric protein intolerance was established. Although the architectural and inflammatory changes are similar to those present in celiac disease, the lamina propria contains less inflammatory cells and the surface epithelium is not damaged despite the increase in intraepithelial lymphocytes. (A, Hematoxylin & eosin, ×125; Insert, hematoxylin & eosin ×50; B, hematoxylin & eosin, ×200).
mmol/L (normal, 10 to 35 mmol/L) was detected. A repeat ammonia level was 120 mmol/L, with normal aminotransferases and normal coagulation profile. Serum glucose was 82 and CO2 was 24. All sources of protein were stopped, and the ammonia level decreased spontaneously to 44 mmol/L. Blood levels of glutamine, asparagine, and alanine were elevated (1830, 130, and 1100 mmol/L, respectively), and generalized aminoaciduria with massive excretion of lysine (2613 mmol/mol creatinine) was detected. Urine orotic acid (658 mmol/mol creatinine) was markedly elevated. These findings, added to the clinical picture, were believed to be consistent with the diagnosis of LPI. Because of the patient’s diarrhea, parenteral nutrition was started to provide adequate energy substrate. The glutenfree diet was continued with protein intake limited to 1 gm/kg per day. Oral citrulline, 150 mg/kg per day was initiated. On this therapy, appetite improved, diarrhea resolved, and the patient was given oral feedings. He was discharged receiving citrulline and a protein-restricted, gluten-free diet. Soon after returning home, the patient began to demand and eat protein-rich foods, including meat, without adverse consequences. Repeat antigliadin and 154
antiendomysium antibodies were negative and gluten was reintroduced into the diet without recurrence of diarrhea or other symptoms. One year after initiation of citrulline therapy, while receiving a 1.5 gm/kg protein diet containing gluten, the child is asymptomatic, his weight is at the 25th percentile, and his height is at the 10th percentile.
DISCUSSION The diagnosis of celiac disease is based on the combination of typical clinical symptoms associated with characteristic small intestinal mucosal abnormalities on histologic examination of intestinal biopsy specimen. Clinical remission on a strict gluten-free diet with relief of all symptoms of the disease is also necessary. Confirmation of the diagnosis is made when a second biopsy specimen shows resolution of histologic findings and reintroduction of gluten causes a clinical or histologic relapse.2,3 Positive serologic markers (antigliadin and antiendomysium antibodies) are advantageous screening tests.4-7 Although our patient lacked positive serologic markers, a tentative diagnosis of celiac disease was made on the basis of the
OF PEDIATRICS JANUARY 1998
constellation of clinical symptoms and typical histologic findings for celiac disease seen in the intestinal biopsy specimen. His failure to improve on a glutenfree diet and the development of frank hyperammonemia on nasogastric tube feeding prompted reassessment of his diagnosis. Retrospectively, his rejection of dietary protein and his diarrhea were manifestations of LPI. Ideally, our patient would have undergone gluten challenge and intestinal biopsy to confirm the absence of celiac disease. We could not recommend repeat biopsy because the child was thriving on a gluten-containing diet with the addition of citrulline. The highly differentiated mucosa of the small intestine responds in a limited number of ways to diverse pernicious stimuli.8,9 Consequently, the histologic findings described in celiac disease have been associated with other conditions, including protein-energy malnutrition, tropical sprue, giardiasis, and acquired hypogammaglobulinemia.8-12 The mucosal changes in all these conditions are reversible after removal of the injurious agent. Interestingly, in a group of patients with kwashiorkor, the histologic findings persisted for more than 1 year after the correction of nutritional deficiencies.7 A patient similar to ours was described by Tarlow et al.13 in 1972. They reported a child with a diagnosis of celiac disease based on intestinal histologic findings who did not respond to a gluten-free diet. Further evaluation led to the diagnosis of Hartnup disorder, an inherited condition characterized by impaired transport of neutral amino acids. We propose that the intestinal mucosal changes seen in our patient and in the patient described by Tarlow et al.13 were caused by severe protein-calorie malnutrition induced by the combination of poor protein intake and diarrheal disease associated with their primary metabolic diseases. LPI represents another entity that can lead to a clinical and histologic picture similar to celiac disease. The literature describes a small number of patients with celiac disease refractory to the gluten-free diet. We suggest that patients with clinical and histologic characteristics of celiac disease, but who are unresponsive to a gluten-free diet, be evaluated for metabolic disorders.
THE JOURNAL OF PEDIATRICS Volume 132, Number 1 We thank Dr. Mendel Tuchman for the invaluable contribution of the definitive metabolic diagnosis of the case presented here.
REFERENCES 1. Simell O. Lysinuric protein intolerance and other cationic aminoacidurias. In: Scriver R, et al., editors. The metabolic and molecular basis of inherited disease. New York: Mc Graw-Hill; 1995. p. 3603-27. 2. Walker JA. Celiac disease. In: Walker A, et al., editors. Pediatric gastrointestinal disease. St. Louis: Mosby–Year Book; 1996. p. 840-61. 3. Report of Working Group of European Society of Paediatric Gastroenterology and Nutrition. Revised criteria for diagnosis of coeliac disease. Arch Dis Child 1990;66:909-11.
DOHIL
4. De Rosa S, Litwin N, de Davila MT, et al. The correlation of IgA-class antigliadin and antiendomysium antibodies (AGA-IgA— Ema-IgA) with the intestinal histology in celiac disease (CD). Acta Gastroenterol Latinoam 1992;22:161-7. 5. Van der Meer BW, Mearin ML, Pena AS, Van Tol MJ, Lamers CB, Dooren LJ. The clinical significance of anti-gliadin antibodies determination in blood of children with suspected celiac disease. Tijdschr Kindergeneeskunde 1993;61:7-12. 6. Vasquez H, Sugai E, Pedreira S, et al. Screening for asymptomatic celiac sprue in families. J. Clin Gastroenterol 1995; 21:130-3. 7. Cataldo F, Ventura A, Lazzari R, et al. Antiendomysium antibodies and coeliac disease: solved and unsolved questions. An Italian multicentre study. Acta Paediatrica 1995;84:1125-31.
ET AL.
8. Stanfield JP, Hutt MSR, Tunnicliffe R. Intestinal biopsy in kwashiorkor. Lancet 1965:2:519-23. 9. Brunser O, Reid A, Monckeberg F, Maccioni A, Contreras I. Jejunal biopsies in infant malnutrition: with special reference to mitotic index. Pediatrics 1966;38:605-11. 10. Geboes K, Ectors N, Desmet VJ. Coeliac disease “anatomic pathology”. Acta Gastroenterol Belg 1992;55:190-9. 11. Thomas AG, Phillips AD, Walker-Smith JA. The value of proximal small intestinal biopsy in the differential diagnosis of chronic diarrhoea. Arch Dis Child 1992;67:741-3. 12. Trier JS. Diagnosis and treatment of celiac sprue. Hosp Pract 1993;28:41-54. 13. Tarlow MJ, Seakins JWT, Lloyd JK, Matthews DM, Cheng B, Thomas AJ. Absorption of amino acids and peptides in a child with a variant of Hartnup disease and coexistent coeliac disease. Arch Dis Child 1972;47:798-803.
R
Recombinant human erythropoietin for treatment of
anemia of chronic disease in children with Crohn’s disease Ranjan Dohil, MB BCh, MRCP(UK), Eric Hassall, MB ChB, FRCP(C), Louis D. Wadsworth, MB ChB, FRCP(C), FRCPath, and David M. Israel, MD, FRCP(C) We evaluated the efficacy and safety of and compliance with rH-EPO (150 U/kg three times a week subcutaneously for up to 12 weeks) for treatment of anemia in childhood Crohn’s disease (n = 4). The mean hemoglobin level before rH-EPO therapy was 109 gm/L (10.9 gm/dl) (range, 103 to 115 gm/L). The mean hemoglobin level in the three compliant children increased to 138 gm/L (13.8 gm/dl) after treatment. Response time for the correction of anemia ranged from 6 to 12 weeks (mean, 9.5 weeks). Resolution of symptoms of lethargy, poor appetite, and irritability occurred with correction of the anemia. The only adverse effect observed was transient local pain at the injection site.(J Pediatr 1998;132:155-9). From the Division of Gastroenterology and Department of Pathology, University of British Columbia and B.C. Children’s Hospital, Vancouver, British Columbia, Canada. Supported by a grant from Ortho-McNeil, North York, Ontario, Canada. Submitted for publication May 6, 1996; accepted Dec. 5, 1996. Reprint requests: David M. Israel, MD, Division of Pediatric Gastroenterology, University of British Columbia, 4480 Oak St., Vancouver, BC, Canada V6H 3V4. Copyright © 1998 by Mosby, Inc. 0022-3476/98/$5.00 + 0 9/22/79704
Crohn’s disease may be complicated by the anemia of chronic disease. ACD is characterized by normochromic, normocytic or mildly microcytic erythrocytes, low or normal serum iron and total ironbinding capacity, normal or increased iron stores reflected by elevated ferritin levels, low transferrin levels, and an inappropriately low reticulocyte response relative to the degree of anemia.1,2 This form of anemia is unresponsive to treatment
with iron, vitamin B12, or folic acid. Anemia per se can cause symptoms such as reduced exercise tolerance, lethargy, irritability, anorexia, and may contribute to poor growth,3 and when severe, may warrant blood transfusion.4 For children with ACD, recombinant human erythropoietin therapy may offer a safer and more physiologic option than blood transfusion. Recombinant human erythropoietin has been used successfully to reverse ACD in adults with rheumatoid arthritis5 and inflammatory bowel disease,6,7 as well as in children with chronic renal failure.8 To our knowledge, there are no published data on the efficacy and safety of rH-EPO in children with inflammatory bowel disease.
ACD Anemia of chronic disease ESR Erythrocyte sedimentation rate rh-EPO Recombinant human erythropoietin
155
Lysinuric protein intolerance masquerading as celiac disease: A case report
Manuel A. Reinoso, MD, Chester Whitley, MD, Jose Jessurun, MD, and Sarah Jane Schwarzenberg, MD
A 5 1/2-year-old boy presented with delayed growth, chronic diarrhea, and hypoproteinemia. Clinical presentation, initial laboratory data, and evaluation of an intestinal biopsy specimen suggested a diagnosis of celiac disease. Symptoms did not resolve on a gluten-free diet. The development of hyperammonemia prompted further studies that led to the diagnosis of lysinuric protein intolerance. Lysinuric protein intolerance, although a rare disorder, should be included in the differential diagnosis of conditions associated with intestinal villous atrophy. ( J Pediatr 1998;132:153-5)
Lysinuric protein intolerance is a rare autosomal recessive disorder in which there is increased urinary excretion and clearance of all cationic amino acids, especially of lysine. Cationic amino acids are also poorly absorbed from the intestine. Patients are usually asymptomatic in infancy, especially when breast-fed, but after weaning symptoms of poor appetite, diarrhea, poor growth, and irritability develop. If untreated, hepatosplenomegaly develops, as well as muscle hypotonia, sparse hair, and osteoporosis. Mental development varies from normal to moderate delay.1 We report a patient with LPI whose clinical presentation and histologic findings on a duodenal biopsy specimen suggested an initial diagnosis of celiac sprue.
CASE
REPORT
A 5 1/2-year-old white boy was seen at the University of Minnesota with complaints of abdominal pain, diarrhea, vomiting, poor appetite, and fatigue for more
than 2 months. The child was reportedly small in stature since early childhood. He had refused meat and dairy products since early life, preferentially eating cereals, vegetables, and yogurt. The rest of his family were meat eaters. An older sibling was growing normally and there were no other family members with similar symptomatology. His parents denied consanguinity. The physical examination was remarkable for pallor, thin and light-colored hair, and pitting edema of lower extremities. His weight of 14.7 kg and height of 98 cm were both below the 5th percentile for his age. There was dry, scaly skin on his ankles and feet and sores in the corners of his mouth. No visceromegaly was detected by examination. Laboratory data were as follows: serum sodium, 132 mmol/L (132 mEq/L); serum total CO2, 24 mmol/L; serum albumin, 17 gm/L (1.7 gm/dl); hemoglobin, 1.4 mmol/ L (9 gm/dl); platelet count, 170 × 109/L (170,000/mm3); prothrombin time, 12.8 sec; serum zinc, 6 mmol/L (39 mg/dl);
From the Department of Pediatrics, Division of Pediatric Gastroenterology and Nutrition, Division of Genetics and Metabolism; the Institute of Human Genetics and Department of Pathology and Laboratory Medicine; University of Minnesota, Minneapolis. Submitted for publication Mar. 18, 1996; accepted Feb. 12, 1997. Reprint requests: Sarah J. Schwarzenberg, MD, Box 185 UMHC, Minneapolis, MN 55455. Copyright © 1998 by Mosby, Inc. 0022-3476/98/$5.00 + 0 9/22/81203
serum iron, 2.3 mmol/L (13 mg/dl); transferrin, 60 mg/dl. Antiendomysium IgA and antigliadin IgA and IgG antibody tests were negative. Total IgA was not measured. Spot stool samples were positive for fecal fat. Urinalysis, thyroid studies, renal function, and aminotransferases were normal. Bone age was delayed more than 2 standard deviations and osteopenia was noted. He was anergic to the tuberculin, Candida, and tetanus skin tests. LPI
Lysinuric protein intolerance
Esophagogastroduodenoscopy with small intestinal biopsy was performed. Histopathologic examination of the fourth portion of the duodenal mucosa showed blunting of villi with elongation of crypts. The surface epithelium showed numerous intraepithelial lymphocytes and shortening of cells. The lamina propria was mildly expanded by plasma cells and lymphocytes (Figure). These changes were interpreted as consistent with celiac disease. The child was started on a gluten-free diet and was discharged home on vitamin K, iron, and zinc replacement therapy. One month later his diarrhea and emesis persisted and he had lost weight. He was admitted and started on nasogastric tube feedings with a complete pediatric liquid formula, Pediasure (Ross Products Division, Abbott Laboratories, Columbus, Ohio). He received 1.9 gm protein/kg per day. Albumin infusions were given, followed by diuretics, to reduce edema. Prednisone at 1 mg/kg per day was started to diminish inflammation. After 24 hours of enteral nutrition, the patient became increasingly irritable, but his level of consciousness was always preserved. An increased ammonia level of 78 153
REINOSO
ET AL.
THE JOURNAL
Figure. The duodenal biopsy specimen showed marked blunting of the villi, elongation of crypts (left), increased number of plasma cells and lymphocytes in the lamina propria, and many intraepithelial lymphocytes (right). This biopsy specimen was reviewed retrospectively after the diagnosis of lysinuric protein intolerance was established. Although the architectural and inflammatory changes are similar to those present in celiac disease, the lamina propria contains less inflammatory cells and the surface epithelium is not damaged despite the increase in intraepithelial lymphocytes. (A, Hematoxylin & eosin, ×125; Insert, hematoxylin & eosin ×50; B, hematoxylin & eosin, ×200).
mmol/L (normal, 10 to 35 mmol/L) was detected. A repeat ammonia level was 120 mmol/L, with normal aminotransferases and normal coagulation profile. Serum glucose was 82 and CO2 was 24. All sources of protein were stopped, and the ammonia level decreased spontaneously to 44 mmol/L. Blood levels of glutamine, asparagine, and alanine were elevated (1830, 130, and 1100 mmol/L, respectively), and generalized aminoaciduria with massive excretion of lysine (2613 mmol/mol creatinine) was detected. Urine orotic acid (658 mmol/mol creatinine) was markedly elevated. These findings, added to the clinical picture, were believed to be consistent with the diagnosis of LPI. Because of the patient’s diarrhea, parenteral nutrition was started to provide adequate energy substrate. The glutenfree diet was continued with protein intake limited to 1 gm/kg per day. Oral citrulline, 150 mg/kg per day was initiated. On this therapy, appetite improved, diarrhea resolved, and the patient was given oral feedings. He was discharged receiving citrulline and a protein-restricted, gluten-free diet. Soon after returning home, the patient began to demand and eat protein-rich foods, including meat, without adverse consequences. Repeat antigliadin and 154
antiendomysium antibodies were negative and gluten was reintroduced into the diet without recurrence of diarrhea or other symptoms. One year after initiation of citrulline therapy, while receiving a 1.5 gm/kg protein diet containing gluten, the child is asymptomatic, his weight is at the 25th percentile, and his height is at the 10th percentile.
DISCUSSION The diagnosis of celiac disease is based on the combination of typical clinical symptoms associated with characteristic small intestinal mucosal abnormalities on histologic examination of intestinal biopsy specimen. Clinical remission on a strict gluten-free diet with relief of all symptoms of the disease is also necessary. Confirmation of the diagnosis is made when a second biopsy specimen shows resolution of histologic findings and reintroduction of gluten causes a clinical or histologic relapse.2,3 Positive serologic markers (antigliadin and antiendomysium antibodies) are advantageous screening tests.4-7 Although our patient lacked positive serologic markers, a tentative diagnosis of celiac disease was made on the basis of the
OF PEDIATRICS JANUARY 1998
constellation of clinical symptoms and typical histologic findings for celiac disease seen in the intestinal biopsy specimen. His failure to improve on a glutenfree diet and the development of frank hyperammonemia on nasogastric tube feeding prompted reassessment of his diagnosis. Retrospectively, his rejection of dietary protein and his diarrhea were manifestations of LPI. Ideally, our patient would have undergone gluten challenge and intestinal biopsy to confirm the absence of celiac disease. We could not recommend repeat biopsy because the child was thriving on a gluten-containing diet with the addition of citrulline. The highly differentiated mucosa of the small intestine responds in a limited number of ways to diverse pernicious stimuli.8,9 Consequently, the histologic findings described in celiac disease have been associated with other conditions, including protein-energy malnutrition, tropical sprue, giardiasis, and acquired hypogammaglobulinemia.8-12 The mucosal changes in all these conditions are reversible after removal of the injurious agent. Interestingly, in a group of patients with kwashiorkor, the histologic findings persisted for more than 1 year after the correction of nutritional deficiencies.7 A patient similar to ours was described by Tarlow et al.13 in 1972. They reported a child with a diagnosis of celiac disease based on intestinal histologic findings who did not respond to a gluten-free diet. Further evaluation led to the diagnosis of Hartnup disorder, an inherited condition characterized by impaired transport of neutral amino acids. We propose that the intestinal mucosal changes seen in our patient and in the patient described by Tarlow et al.13 were caused by severe protein-calorie malnutrition induced by the combination of poor protein intake and diarrheal disease associated with their primary metabolic diseases. LPI represents another entity that can lead to a clinical and histologic picture similar to celiac disease. The literature describes a small number of patients with celiac disease refractory to the gluten-free diet. We suggest that patients with clinical and histologic characteristics of celiac disease, but who are unresponsive to a gluten-free diet, be evaluated for metabolic disorders.
THE JOURNAL OF PEDIATRICS Volume 132, Number 1 We thank Dr. Mendel Tuchman for the invaluable contribution of the definitive metabolic diagnosis of the case presented here.
REFERENCES 1. Simell O. Lysinuric protein intolerance and other cationic aminoacidurias. In: Scriver R, et al., editors. The metabolic and molecular basis of inherited disease. New York: Mc Graw-Hill; 1995. p. 3603-27. 2. Walker JA. Celiac disease. In: Walker A, et al., editors. Pediatric gastrointestinal disease. St. Louis: Mosby–Year Book; 1996. p. 840-61. 3. Report of Working Group of European Society of Paediatric Gastroenterology and Nutrition. Revised criteria for diagnosis of coeliac disease. Arch Dis Child 1990;66:909-11.
DOHIL
4. De Rosa S, Litwin N, de Davila MT, et al. The correlation of IgA-class antigliadin and antiendomysium antibodies (AGA-IgA— Ema-IgA) with the intestinal histology in celiac disease (CD). Acta Gastroenterol Latinoam 1992;22:161-7. 5. Van der Meer BW, Mearin ML, Pena AS, Van Tol MJ, Lamers CB, Dooren LJ. The clinical significance of anti-gliadin antibodies determination in blood of children with suspected celiac disease. Tijdschr Kindergeneeskunde 1993;61:7-12. 6. Vasquez H, Sugai E, Pedreira S, et al. Screening for asymptomatic celiac sprue in families. J. Clin Gastroenterol 1995; 21:130-3. 7. Cataldo F, Ventura A, Lazzari R, et al. Antiendomysium antibodies and coeliac disease: solved and unsolved questions. An Italian multicentre study. Acta Paediatrica 1995;84:1125-31.
ET AL.
8. Stanfield JP, Hutt MSR, Tunnicliffe R. Intestinal biopsy in kwashiorkor. Lancet 1965:2:519-23. 9. Brunser O, Reid A, Monckeberg F, Maccioni A, Contreras I. Jejunal biopsies in infant malnutrition: with special reference to mitotic index. Pediatrics 1966;38:605-11. 10. Geboes K, Ectors N, Desmet VJ. Coeliac disease “anatomic pathology”. Acta Gastroenterol Belg 1992;55:190-9. 11. Thomas AG, Phillips AD, Walker-Smith JA. The value of proximal small intestinal biopsy in the differential diagnosis of chronic diarrhoea. Arch Dis Child 1992;67:741-3. 12. Trier JS. Diagnosis and treatment of celiac sprue. Hosp Pract 1993;28:41-54. 13. Tarlow MJ, Seakins JWT, Lloyd JK, Matthews DM, Cheng B, Thomas AJ. Absorption of amino acids and peptides in a child with a variant of Hartnup disease and coexistent coeliac disease. Arch Dis Child 1972;47:798-803.
R
Recombinant human erythropoietin for treatment of
anemia of chronic disease in children with Crohn’s disease Ranjan Dohil, MB BCh, MRCP(UK), Eric Hassall, MB ChB, FRCP(C), Louis D. Wadsworth, MB ChB, FRCP(C), FRCPath, and David M. Israel, MD, FRCP(C) We evaluated the efficacy and safety of and compliance with rH-EPO (150 U/kg three times a week subcutaneously for up to 12 weeks) for treatment of anemia in childhood Crohn’s disease (n = 4). The mean hemoglobin level before rH-EPO therapy was 109 gm/L (10.9 gm/dl) (range, 103 to 115 gm/L). The mean hemoglobin level in the three compliant children increased to 138 gm/L (13.8 gm/dl) after treatment. Response time for the correction of anemia ranged from 6 to 12 weeks (mean, 9.5 weeks). Resolution of symptoms of lethargy, poor appetite, and irritability occurred with correction of the anemia. The only adverse effect observed was transient local pain at the injection site.(J Pediatr 1998;132:155-9). From the Division of Gastroenterology and Department of Pathology, University of British Columbia and B.C. Children’s Hospital, Vancouver, British Columbia, Canada. Supported by a grant from Ortho-McNeil, North York, Ontario, Canada. Submitted for publication May 6, 1996; accepted Dec. 5, 1996. Reprint requests: David M. Israel, MD, Division of Pediatric Gastroenterology, University of British Columbia, 4480 Oak St., Vancouver, BC, Canada V6H 3V4. Copyright © 1998 by Mosby, Inc. 0022-3476/98/$5.00 + 0 9/22/79704
Crohn’s disease may be complicated by the anemia of chronic disease. ACD is characterized by normochromic, normocytic or mildly microcytic erythrocytes, low or normal serum iron and total ironbinding capacity, normal or increased iron stores reflected by elevated ferritin levels, low transferrin levels, and an inappropriately low reticulocyte response relative to the degree of anemia.1,2 This form of anemia is unresponsive to treatment
with iron, vitamin B12, or folic acid. Anemia per se can cause symptoms such as reduced exercise tolerance, lethargy, irritability, anorexia, and may contribute to poor growth,3 and when severe, may warrant blood transfusion.4 For children with ACD, recombinant human erythropoietin therapy may offer a safer and more physiologic option than blood transfusion. Recombinant human erythropoietin has been used successfully to reverse ACD in adults with rheumatoid arthritis5 and inflammatory bowel disease,6,7 as well as in children with chronic renal failure.8 To our knowledge, there are no published data on the efficacy and safety of rH-EPO in children with inflammatory bowel disease.
ACD Anemia of chronic disease ESR Erythrocyte sedimentation rate rh-EPO Recombinant human erythropoietin
155