+Model
ARTICLE IN PRESS
CLINRE-702; No. of Pages 2
Clinics and Research in Hepatology and Gastroenterology (2015) xxx, xxx.e1—xxx.e2
Available online at
ScienceDirect www.sciencedirect.com
LETTER TO THE EDITOR
Schwachman—Diamond syndrome: Increased risk for autoimmune diseases? Schwachman—Diamond syndrome: increased risk for autoimmune diseases? Schwachman—Diamond syndrome (SDS) is a rare autosomal recessive disease which most commonly presents with exocrine pancreatic dysfunction and bone marrow failure in early childhood. Clinical features include hematological abnormalities (neutropenia 98%, anemia 42%, thrombocytopenia 34%, and pancytopenia 19%), increased risk of myelodysplastic syndrome and acute myelogenous leukemia, poor growth, frequent infections, hepatic abnormalities, developmental abnormalities, and skeletal abnormalities including metaphyseal dysostosis, thoracic dystrophies and osteopenia [1—5]. Autoimmune enteropathy (AIE) is a disease of infancy associated with malabsorption, chronic diarrhea and intestinal mucosal damage. Anti-enterocyte and anti-goblet cell antibodies have been implied in the pathogenesis but they are not always required for establishing the diagnosis [6]. Herein, we report a 36-year-old patient with a clinically established diagnosis of Schwachman—Diamond syndrome who presented with intractable diarrhea unresponsive to pancreatic enzyme replacement and loperamide, and later diagnosed as autoimmune enteropathy. To our knowledge, although there are two reports in the literature showing the association of SDS with autoimmune diseases, this is the first report showing the autoimmune enteropathy in a case with SDS. Thirty-six-year-old female, with mild intellectual disability, presented with chronic diarrhea, iron deficiency, and left upper quadrant pain. She had been suffering from these complaints for the past 20 years with occasional exacerbations. The patient had a clinically established diagnosis of SDS for which she used pancreatic enzymes for an extended period of time with little improvement. The patient described having watery stools up to 8 times per day with no blood and mucus in it and no response to loperamide. Stool was foul smelling and associated with intermittent left upper quadrant pain, which is severe, lasting for hours and not associated with nausea or vomiting.
History was significant for osteoporosis, anemia (unresponsive to iron and B12 supplementation), and hypothyroidism. Review of systems revealed occasional facial flushing. Previous surgical history includes cholecystectomy and extraction of all teeth due to dental caries. An intestinal biopsy was performed and showed a marked goblet cell depletion with crypt apoptosis and mild acute inflammation suggestive of autoimmune enteropathy (AIE). Prednisone was started, but was not successful. Abdominal computerized tomography (CT) studies revealed mild fluid distention with no abnormally, dilated loops, and pericolonic stranding suggestive of acute inflammation. Celiac serology and ANA were all negative. Stool culture, VIP levels, Clostridium difficile testing were all negative. The repeat biopsy demonstrated pathological changes consistent with intestinal goblet cell autoantibody-associated enteropathy. Genetic analyses revealed a heterozygous mutation in the SBDS gene, confirming the previously clinically established diagnosis. Our patient was started on budenoside and showed mild improvement. Diphenoxylate/atropin, azathioprine and other immunosuppressive therapies are also considered in the therapy of AIE. At first, Reif et al. suggested an association between SDS and autoimmunity in 1990; and reported development of autoimmune thyroiditis in a 2-year-old boy with SDS [7]. Secondly, Veropalumbo et al. reported two SDS cases with antigliadin antibody positive inflammatory enteropathy and antismooth muscle and/or antinuclear antibody positive autoimmune-like liver disease in 2014 [8]. Our report is the first reported case of steroid resistant AIE with concomitant SDS. In SDS patients with chronic diarrhea AIE must be considered in the differential diagnosis. It has been shown that SDS has a defective marrow microenvironment and aberrant marrow progenitors tending to develop myelodysplasia and aplastic anemia, but there is no data regarding a tendency to autoimmunity in SDS [9]. Further investigation into the causal link between autoimmunity and SDS is warranted for a clear understanding of SDS and development of more specific therapies for such cases.
Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
http://dx.doi.org/10.1016/j.clinre.2014.12.006 2210-7401/© 2015 Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Roach EC, et al. Schwachman—Diamond syndrome: Increased risk for autoimmune diseases? Clin Res Hepatol Gastroenterol (2015), http://dx.doi.org/10.1016/j.clinre.2014.12.006
+Model CLINRE-702; No. of Pages 2
ARTICLE IN PRESS
xxx.e2
References [1] Smith OP, Hann IM, Chessells JM, Reeves BR, Milla P. Haematological abnormalities in Schwachman—Diamond syndrome. Br J Haematol 1996;94:279—84. [2] Ginzberg H, Shin J, Ellis L, Goobie S, Morrison J, Corey M, et al. Schwachman syndrome: phenotypic manifestations of sibling sets and isolated cases in a large patient cohort are similar. J Pediatr 1999;135:81—8. [3] Toiviainen-Salo S, Mayranpaa MK, Durie PR, Richards N, Grynpas M, Ellis L, et al. Schwachman—Diamond syndrome is associated with low-turnover osteoporosis. Bone 2007;41:965—72. [4] Makitie O, Ellis L, Durie PR, Morrison JA, Sochett EB, Rommens JM, et al. Skeletal phenotype in patients with Schwachman-Diamond syndrome and mutations in SBDS. Clin Genet 2004;65:101—12. [5] Kerr EN, Ellis L, Dupuis A, Rommens JM, Durie PR. The behavioral phenotype of school-age children with Schwachman—Diamond syndrome indicates neurocognitive dysfunction with loss of Schwachman—Bodian—Diamond syndrome gene function. J Pediatr 2010;156:433—8. [6] Akram S, Murray JA, Pardi DS, Alexander GL, Schaffner JA, Russo PA, et al. Adult autoimmune enteropathy: Mayo Clinic Rochester experience. Clin Gastroenterol Hepatol 2007;5:1282—90 [quiz 1245]. [7] Reif S, Arav-Boger R, Diamant S, Burstein Y, Fatal A. Schwachman—Diamond syndrome associated with autoimmune phenomena. J Med 1999;30:259—65.
Letter to the Editor [8] Veropalumbo C, Campanozzi A, De Gregorio F, Correra A, Raia V, Vajro P. Schwachman—Diamond syndrome with autoimmune-like liver disease and enteropathy mimicking celiac disease. Clin Res Hepatol Gastroenterol 2014;8(13), http://dx.doi.org/10.1016/j.clinre.2014.06.017. [9] Dror Y, Freedman MH. Schwachman—Diamond syndrome: an inherited proleukemic bone marrow failure disorder with aberrant hematopoetic progenitors and faulty marrow microenvironment. Blood 1999;94:3048—54.
Emir Charles Roach a May Olayan b Ozan Unlu a,∗ Caner Saygin a Abdullah Shatnawei c a Cleveland Clinic, Department of Pathobiology, 9500 Euclid Avenue, Cleveland, 44106 Ohio, USA b Cleveland Clinic, Fairview Hospital, Department of Internal Medicine, 9500 Euclid Avenue, Cleveland, 44106 Ohio, USA c Cleveland Clinic, Department of Gastroenterology and Hepatology, 9500 Euclid Avenue, Cleveland, 44106 Ohio, USA ∗ Corresponding author. E-mail address: [email protected] (O. Unlu)
Please cite this article in press as: Roach EC, et al. Schwachman—Diamond syndrome: Increased risk for autoimmune diseases? Clin Res Hepatol Gastroenterol (2015), http://dx.doi.org/10.1016/j.clinre.2014.12.006
ARTICLE IN PRESS
CLINRE-702; No. of Pages 2
Clinics and Research in Hepatology and Gastroenterology (2015) xxx, xxx.e1—xxx.e2
Available online at
ScienceDirect www.sciencedirect.com
LETTER TO THE EDITOR
Schwachman—Diamond syndrome: Increased risk for autoimmune diseases? Schwachman—Diamond syndrome: increased risk for autoimmune diseases? Schwachman—Diamond syndrome (SDS) is a rare autosomal recessive disease which most commonly presents with exocrine pancreatic dysfunction and bone marrow failure in early childhood. Clinical features include hematological abnormalities (neutropenia 98%, anemia 42%, thrombocytopenia 34%, and pancytopenia 19%), increased risk of myelodysplastic syndrome and acute myelogenous leukemia, poor growth, frequent infections, hepatic abnormalities, developmental abnormalities, and skeletal abnormalities including metaphyseal dysostosis, thoracic dystrophies and osteopenia [1—5]. Autoimmune enteropathy (AIE) is a disease of infancy associated with malabsorption, chronic diarrhea and intestinal mucosal damage. Anti-enterocyte and anti-goblet cell antibodies have been implied in the pathogenesis but they are not always required for establishing the diagnosis [6]. Herein, we report a 36-year-old patient with a clinically established diagnosis of Schwachman—Diamond syndrome who presented with intractable diarrhea unresponsive to pancreatic enzyme replacement and loperamide, and later diagnosed as autoimmune enteropathy. To our knowledge, although there are two reports in the literature showing the association of SDS with autoimmune diseases, this is the first report showing the autoimmune enteropathy in a case with SDS. Thirty-six-year-old female, with mild intellectual disability, presented with chronic diarrhea, iron deficiency, and left upper quadrant pain. She had been suffering from these complaints for the past 20 years with occasional exacerbations. The patient had a clinically established diagnosis of SDS for which she used pancreatic enzymes for an extended period of time with little improvement. The patient described having watery stools up to 8 times per day with no blood and mucus in it and no response to loperamide. Stool was foul smelling and associated with intermittent left upper quadrant pain, which is severe, lasting for hours and not associated with nausea or vomiting.
History was significant for osteoporosis, anemia (unresponsive to iron and B12 supplementation), and hypothyroidism. Review of systems revealed occasional facial flushing. Previous surgical history includes cholecystectomy and extraction of all teeth due to dental caries. An intestinal biopsy was performed and showed a marked goblet cell depletion with crypt apoptosis and mild acute inflammation suggestive of autoimmune enteropathy (AIE). Prednisone was started, but was not successful. Abdominal computerized tomography (CT) studies revealed mild fluid distention with no abnormally, dilated loops, and pericolonic stranding suggestive of acute inflammation. Celiac serology and ANA were all negative. Stool culture, VIP levels, Clostridium difficile testing were all negative. The repeat biopsy demonstrated pathological changes consistent with intestinal goblet cell autoantibody-associated enteropathy. Genetic analyses revealed a heterozygous mutation in the SBDS gene, confirming the previously clinically established diagnosis. Our patient was started on budenoside and showed mild improvement. Diphenoxylate/atropin, azathioprine and other immunosuppressive therapies are also considered in the therapy of AIE. At first, Reif et al. suggested an association between SDS and autoimmunity in 1990; and reported development of autoimmune thyroiditis in a 2-year-old boy with SDS [7]. Secondly, Veropalumbo et al. reported two SDS cases with antigliadin antibody positive inflammatory enteropathy and antismooth muscle and/or antinuclear antibody positive autoimmune-like liver disease in 2014 [8]. Our report is the first reported case of steroid resistant AIE with concomitant SDS. In SDS patients with chronic diarrhea AIE must be considered in the differential diagnosis. It has been shown that SDS has a defective marrow microenvironment and aberrant marrow progenitors tending to develop myelodysplasia and aplastic anemia, but there is no data regarding a tendency to autoimmunity in SDS [9]. Further investigation into the causal link between autoimmunity and SDS is warranted for a clear understanding of SDS and development of more specific therapies for such cases.
Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.
http://dx.doi.org/10.1016/j.clinre.2014.12.006 2210-7401/© 2015 Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Roach EC, et al. Schwachman—Diamond syndrome: Increased risk for autoimmune diseases? Clin Res Hepatol Gastroenterol (2015), http://dx.doi.org/10.1016/j.clinre.2014.12.006
+Model CLINRE-702; No. of Pages 2
ARTICLE IN PRESS
xxx.e2
References [1] Smith OP, Hann IM, Chessells JM, Reeves BR, Milla P. Haematological abnormalities in Schwachman—Diamond syndrome. Br J Haematol 1996;94:279—84. [2] Ginzberg H, Shin J, Ellis L, Goobie S, Morrison J, Corey M, et al. Schwachman syndrome: phenotypic manifestations of sibling sets and isolated cases in a large patient cohort are similar. J Pediatr 1999;135:81—8. [3] Toiviainen-Salo S, Mayranpaa MK, Durie PR, Richards N, Grynpas M, Ellis L, et al. Schwachman—Diamond syndrome is associated with low-turnover osteoporosis. Bone 2007;41:965—72. [4] Makitie O, Ellis L, Durie PR, Morrison JA, Sochett EB, Rommens JM, et al. Skeletal phenotype in patients with Schwachman-Diamond syndrome and mutations in SBDS. Clin Genet 2004;65:101—12. [5] Kerr EN, Ellis L, Dupuis A, Rommens JM, Durie PR. The behavioral phenotype of school-age children with Schwachman—Diamond syndrome indicates neurocognitive dysfunction with loss of Schwachman—Bodian—Diamond syndrome gene function. J Pediatr 2010;156:433—8. [6] Akram S, Murray JA, Pardi DS, Alexander GL, Schaffner JA, Russo PA, et al. Adult autoimmune enteropathy: Mayo Clinic Rochester experience. Clin Gastroenterol Hepatol 2007;5:1282—90 [quiz 1245]. [7] Reif S, Arav-Boger R, Diamant S, Burstein Y, Fatal A. Schwachman—Diamond syndrome associated with autoimmune phenomena. J Med 1999;30:259—65.
Letter to the Editor [8] Veropalumbo C, Campanozzi A, De Gregorio F, Correra A, Raia V, Vajro P. Schwachman—Diamond syndrome with autoimmune-like liver disease and enteropathy mimicking celiac disease. Clin Res Hepatol Gastroenterol 2014;8(13), http://dx.doi.org/10.1016/j.clinre.2014.06.017. [9] Dror Y, Freedman MH. Schwachman—Diamond syndrome: an inherited proleukemic bone marrow failure disorder with aberrant hematopoetic progenitors and faulty marrow microenvironment. Blood 1999;94:3048—54.
Emir Charles Roach a May Olayan b Ozan Unlu a,∗ Caner Saygin a Abdullah Shatnawei c a Cleveland Clinic, Department of Pathobiology, 9500 Euclid Avenue, Cleveland, 44106 Ohio, USA b Cleveland Clinic, Fairview Hospital, Department of Internal Medicine, 9500 Euclid Avenue, Cleveland, 44106 Ohio, USA c Cleveland Clinic, Department of Gastroenterology and Hepatology, 9500 Euclid Avenue, Cleveland, 44106 Ohio, USA ∗ Corresponding author. E-mail address: [email protected] (O. Unlu)
Please cite this article in press as: Roach EC, et al. Schwachman—Diamond syndrome: Increased risk for autoimmune diseases? Clin Res Hepatol Gastroenterol (2015), http://dx.doi.org/10.1016/j.clinre.2014.12.006
