The Malabsorption Syndrome versus Celiac Disease: A Diagnostic Reappraisal

Andrej Beseda¹, Marián Bencat¹, Lubica Korinkova¹, Janka Papanová¹ and Julius Rajcani^1,

¹Pathology, Diagnostic center, Alpha medical Ltd, Martin, Slovakia

Cite this paper:
Andrej Beseda, Marián Bencat, Lubica Korinkova, Janka Papanová and Julius Rajcani. The Malabsorption Syndrome versus Celiac Disease: A Diagnostic Reappraisal. International Journal of Celiac Disease. 2015; 3(4):118-131. doi: 10.12691/ijcd-3-4-5

Abstract

The most frequent cause of malabsorption syndrome (MAS) in developed countries is the celiac disease (CD). There are two possible approaches for exact diagnostic of this disorder: in case of full blown clinical symptoms the golden standard is duodenal biopsy. When it shows classical mucosa lesions (Marsh type 3 mucosa atrophy of various grades), the diagnosis of CD is confirmed. However, if intraepithelial lymphocyte infiltration (IEL) and/or hyperplastic crypts can be seen in the absence of mucosa atrophy (Marsh type 1 and/or 2 lesions) only, it is reasonable to examine the serologic markers. The most frequent enzyme linked immunosorbent assay (ELISA) tests are: detection of tissue transglutaminase 2 antibody (anti-tTGase 2, especially of IgA class) and the deamidated gliadin peptide antibody (anti-DGP) assay. A simpler serological test, useful for screening, is the detection of anti-endomysium antibody (AEmA) by indirect fluorescent antibody (IFA) in monkey intestine or esophagus sections. This is reasonable to combine with the microdot test for anti-gliadin antibody (AGA), especially by using the endomysium/gliadin mosaic kit (Euroimmun). Taken together, at least three serological markers (anti-tTGase 2, anti-DGP and AGA) are highly specific for CD; their detection first (i.e. prior to duodenal biopsy) is recommended in children as well as in adults showing atypical, silent and or latent forms of CD. In both of them, serology represents a reliable non-invasive approach, which allows precise diagnosis with a probability of nearly 90 %. Another advantage of the non-invasive serological technic is that it can be easily repeated when following the outcome of gluten-free diet (GFD). Nevertheless, duodenal biopsy should be performed in any case, if the serology does not correlate with clinical symptoms. In such patients as well as in those revealing positive serology but negative and/or non-specific histology, immunogenetic typing should be performed in order to assess the expression of DQ2 [DQA*0501-DQB*0201] or DQ8 [DQA*0301-DQB1*0302] haplotypes of the human leukocyte antigen (HLA) class II region critical for the development of CD.

Keywords:
malabsorption syndrome celiac disease gluten sensitivity diagnostic duodenal biopsy serological markers

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Figures

References:

[1]	Mohan H. The Gastrointestinal Tract, In: Textbook of Pathology, 6th Ed., Jaypee Brothers Medical Publishers Ltd, 2010.
[2]	Mathan VI, Baker SJ. Epidemic tropical sprue and other epidemics of diarrhea in South Indian villages. Am J clin Nutr 1968; 21: 1077-1087.
[3]	Ranjan P, Ghoshal UC, Aggarwal R, Pandey R, Misra A et al. Etiological spectrum of sporadic malabsorption syndrome in northern Indian adults at a tertiary hospital." Indian J Gastroenterol 2004; 23:94-98.
[4]	Lindenbaum J, Alam AK, Kent TH. Subclinical small intestinal disease in East Pakistan. Br Med J 1966; 2:1616-1619.
[5]	Wilde H. Tropical sprue in Thailand. J Med Ass Thai 1974; 57:32-40.
[6]	Kirchgatterer A, Allinger S, Balon R, Tuppy H, Knoflach P. Tropical sprue as the cause of chronic diarrhea after travel in Southern Asia. Zschr Gastroenterol 1998; 36:897-900.
[7]	Bayless TM, Wheby MS, Swanson VL. Tropical sprue in Puerto Rico. Am J Clin Nutr 1968; 21:1030-1041.
[8]	Montgomery RD, Chesner IM. Postinfective malabsorption in the temperate zone. Trans Soc Trop Med Hyg 1985; 79:322-327.
[9]	Thabane M, Marshall JK. Post-infectious irritable bowel syndrome. World J Gastroenterol. 2009; 15:3591-3596.
[10]	Ghoshal UC, Park H, Gwee KA. Bugs and irritable bowel syndrome: the good, the bad and the ugly. J Gastroenterol Hepatol 2010; 25:244-251.
[11]	Drasar BS, Shiner M, McLeod GM. Studies on the intestinal flora. I. The bacterial flora of the gastrointestinal tract in healthy and achlorhydric persons. Gastroenterology 1969; 56:71-79.
[12]	Gorbach SL. Intestinal microflora. Gastroenterology 1971; 60: 1110-1129.
[13]	Vantrappen G, Janssens J, Hellemans J, et al. The interdigestive motor complex of normal subjects and patients with bacterial overgrowth of the small intestine. J Clin Invest 1977; 59: 1158-1156.
[14]	Simon GL, Gorbach SL. Intestinal flora in health and disease. Gastroenterology 1984; 86:174-193.
[15]	Husebye E, Skar V, Hoverstad T, et al. Abnormal intestinal motor patterns explain enteric colonization with gram-negative bacilli in late radiation enteropathy. Gastroenterology 1995; 109:1078-1089.
[16]	Yakoob J, Abbas Z, Khan R, Hamid S, Awan S, Jafri W. Small intestinal bacterial overgrowth and lactose intolerance contribute to irritable bowel syndrome symptomatology in Pakistan. Saudi J Gastroenterol 2011; 17:371-375.
[17]	Posserud I, Stotzer PO, Bjoernsson E-S, Abrahamsson H, Simren M. Small intestinal bacterial overgrowth in patients with irritable bowel syndrome. Gut 2007; 56:802-808.
[18]	Ghoshal UC, Ghoshal U, Misra A, Choudhuri G. Partially responsive celiac disease resulting from small intestinal bacterial overgrowth and lactose intolerance. BMC Gastroenterol. 2004; 4: 10.
[19]	Ghoshal UC, Ranjan P. Post-infectious irritable bowel syndrome: the past, the present and the future. J Gastroenterol Hepatol. 2011; 26 (Suppl 3):94-101.
[20]	Kagnoff MF. Celiac disease: pathogenesis of a model immunogenetic disease. J Clin Investigation 2007, vol. 117 Number 1, http://www.jci.org.
[21]	Ghoshal UC, Mehrotra M, Kumar S, Ghoshal U, Krishnani N et al. Spectrum of malabsorption syndrome among adults and factors differentiating celiac disease and tropical malabsorption. Indian J Med Res. 2012; 136:451-459.
[22]	Brown IS, Bettington A, Bettington M, Rosty C. Tropical sprue: revisiting an underecognized disease. Am J Surg Pathol. 2014; 38: 666-672.
[23]	No authors listed. Revised criteria for diagnosis of celiac disease. Report of working group of European Society of Pediatric Gastroenterology and Nutrition. Arch Dis Child. 1990; 65:909-911.
[24]	Brusca I. Overview of biomarkers for diagnosis and monitoring of celiac disease. Adv clin Chem 2015; 68:1-55.
[25]	Makovický P, Rimárová K, Boor A, Makovický P, Vodička P et al., Correlation between antibodies and histology in celiac disease: Incidence of celiac disease is higher than expected in the pediatric population. Molec Med Reports 2013; 8: 1079-1083.
[26]	Adamkov, M, Boselova, L. Digestive system (alimentary canal), pp.221-250 In: Adamkov M (ed.) Introduction to functional histology, (textbook) P + M Turany 2011, www.p--mtlac.sk.
[27]	Rauhavirta T, Lindfors, K, Koskinen O, Laurila K, Kurppa K et al. Impaired epithelial integrity in the duodenal mucosa in early stages of celiac disease. Transl Res 2014; 164: 223-231.
[28]	Villanacci V, Ceppa P, Tavani E, Vindigni C, Volta U. Coeliac disease: the histology report. Dig Liver Dis 2011; 43:S385-395.
[29]	Marsh, MN, Crowe PT. Morphology of mucosal lesion in gluten sensitivity. Baillier’s Clin Gastenterol 1995; 9: 273-293.
[30]	Mino M, Lauwers GY. Role of lymphocyte immunophenotyping in the diagnosis of gluten-sensitive enteropathy with preserved villous architecture. Am J Surg Pathol 2003; 27:1237-1242.
[31]	Kakar S, Nehra V, Murray JA, Dayharsh, GA, Burgart LJ. Significance of intraepithelial lymphocytosis in small bowel biopsy samples with normal mucosal architecture. Am J Gastroenterol. 2003; 98: 2027-2033.
[32]	Settakorn J, Leong AS. Immunohistologic parameters in minimal morphologic change duodenal biopsies from patients with clinically suspected gluten-sensitive enteropathy. Appl Immunohistochem Mol Morphol 2004; 12:198-204.
[33]	Hudacko R, Zhou X-K, Yantiss RK. Immunohistochemical stains for CD3 and CD8 do not improve detection of gluten-sensitive enteropaty in duodenal biopsies. Modern Pathol 2013; 26: 1241-1245.
[34]	Chang F, Mahadeva U, Deere H. Pathological and clinical significance of increased intraepithelial lymphocytes (IELs) in small bowel mucosa. APMIS 2005; 113:385-399.
[35]	Salmi TT, Collin P, Reunala T, Mäki M, Kaukinen K. Diagnostic methods beyond conventional histology in coeliac disease diagnosis. Dig Liver Dis 2010; 42: 28-32.
[36]	Lindfors K, Koskinen O, Kaukinen K. An update on the diagnostics of celiac disease. Int Rev Immunol 2011; 30:185-196.
[37]	Husby S, Koletzko S, Korponay-Szabo´ IR, Mearin ML, Phillips A, et al. European Society for Pediatric Gastroenterology, Hepatology and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr 2012; 54:136-160.
[38]	Ludvigsson JF, Bai JC, Biagi F, Card TR, Ciacci C , et al., (24 auhtors of the BSG Coeliac Disease Guidelines Development Group. Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology. Gut 2014; 63:1210-1228.
[39]	Fernandes-Banares, F, CarrascoA, Garcıa-Puig R, Rosinach M, Gonzalez C et al. Intestinal Intraepithelial Lymphocyte Cytometric Pattern Is More Accurate than Subepithelial Deposits of Anti-Tissue Transglutaminase IgA for the Diagnosis of Celiac Disease in Lymphocytic Enteritis. PLOS ONE 2014; 9:e101249.
[40]	Lee SK, Lo W, Memeo L, Rotterdam H, Green PH. Duodenal histology in patients with celiac disease after treatment with a gluten-free diet. Gastrointest Endocs 2003; 57:187-191.
[41]	Tuire I, Marja-Leena L, Teea S, Katri H, Jukka P et al. Persistent duodenal intraepithelial lymphocytosis despite a long-term strict gluten-free diet in celiac disease. Am J Gastroenterol. 2012; 107:1563-1569.
[42]	Ierardi E, Losurdo G, Piscitelli D, Giorgio F, Sorrentino C et al. Seronegative celiac disease: where is the specific setting? Gastroenterology and Hepatology From Bed to Bench. ©2015 RIGLD, Research Institute for Gastroenterology and Liver Diseases.
[43]	Rostom A, Murray JF, Kagnoff MF. American Gastroenterological Association (AGA): Institute Technical Review on the Diagnosis and Management of Celiac Disease. Gastroenterology 2006; 131:1981-2002.
[44]	Plank, L. Primary Intestinal Malignant Lymphomas Associated With Celiakia – A Pathologist´s Review. International Journal of Celiac Disease 2015;3:59-68.
[45]	Müller-Hermelink, H.K., Delabie, J., Ko, Y.H., Jaffe, E.S., Nakamura, S, T-cell lymphoma of the small intestine, IARC, Lyon, 2010, 112-114.
[46]	Caruso R, Mafini I, delVecchio Blanco D, Fina D, Paoluzi OA et al. Sampling of proximal and distal biopsies in the diagnosis and monitoring of celiac disease. Dig Liver Dis 2014; 46: 323-329.
[47]	Marsh MN. Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity ('celiac sprue'). Gastroenterology 1992; 102:330-354.
[48]	Ofei S, Boyle B, Ediger T, Hill I. Adherence to Endoscopy Biopsy Guidelines for Celiac Disease: A Pediatric Institutional Analysis. J Pediatr Gastroenterol Nutr. 2015 Apr 24; in press.
[49]	Sullivan KE, Magira EE. Immunogenetics, pp.367-386, In: Bellanti JA, Escobar-Gutiérez, A, Tsokos GC (Eds). Immunology (IV): Clinical Applications in Health and Disease. I Care Press, Bethesda, MD, 2012.
[50]	Setty M1, Hormaza L, Guandalini S. Celiac disease: risk assessment, diagnosis odstrániť čiarku, and monitoring. Mol Diagn Ther. 2008; 12:289-298.
[51]	Shuppan D, Junker Y, Barisani D. Celiac disease: from pathogenesis to novel therapy. Gastroenterology 2009; 137: 1912-1933.
[52]	Rubio-Tapia, A., and Murray, J. Celiac Disease. Curr Opin Gastroenterol 2010; 26:116-122.
[53]	Chorzelski, TP., Sulej, J., Tchorzewska, H., Jablonska, S., Beutner, EH. Kumar V.. IgA class endomysium antibodies in dermatitis herpetiformis and coeliac disease. Ann NY Acad Sci 1983; 420: 325-334.
[54]	Calvani, M. Jr, Parisi, G, Miotti, AM, Alessandri, C., Notarnicola, MA. Anti-endomysium antibodies: a new marker for the diagnosis and treatment of celiac disease. Pediatr Med Chir 1992; 14:33-36.
[55]	Mascart-Leone F, Lambrechts A. Serology of celiac disease: early diagnosis and therapeutic impact. Acta Gastroenterol Belg 1995; 58:388-396.
[56]	Nandiwada, S.L., and Tebo, A.E. Testing for antireticulin antibodies in patients with celiac disease is obsolete: a review of recommendations for serologic screening and the literature. Clin Vaccine Immunol 2013; 20:447-450.
[57]	Rujner J, Socha J, Barra E, Gregorek H, Madaliński K et al. Serum and salivary antigliadin antibodies and serum IgA anti-endomysium antibodies as a screening test for coeliac disease. Acta Paediatr. 1996; 85:814-817.
[58]	Maiuri L, Ciacci C, Ricciardelli I, Vacca L, Raia V et al. Unexpected role of surface transglutaminase type II in celiac disease. Gastroenterology 2005; 129:1400-1413.
[59]	Dieterich, W., Ehnis, T., Bauer, M., Donner, P., Volta, U., Riecken, EO. and Schuppan, D. Identification of tissue transglutaminase as the autoantigen of celiac disease. Nat Med 1997; 3:797-801.
[60]	Stern M and Working group on serologic screening for celiac disease. Comparative evaluation of serologic tests for celiac disease. J Pediatr Gastroenterol Nutr 2000; 31:513-519.
[61]	Veermersch P, Geboes K, Marien G, Hoffman I, Hiele M, Bossuyt X. Defining thresholds of antibody levels improves diagnosis of celiac disease. Clin Gastroenterol hepatol 2013; 11:398-403.
[62]	Rajčáni J, Korinkova, L, Bencat M. Detection of autoantibodies by indirect immunofluorescence and related techniques: the pathologist´s view. Medical Research Archives 2015; 4:in press.
[63]	Kuna AT. Serological markers of inflammatory bowel disease. Biochemia Medica 2013; 3:23-42.
[64]	Nakamura RMI, Matsutani M, Barry M. Advances in clinical laboratory tests for inflammatory bowel disease. Clin Chim Acta 2003; 335:9-20.
[65]	Stoecker, W., Teegen, B. Probst C et al. CUZD and GP2 are the exocrine pancreas autoantigens in Crohn´s disease, pp.463-473. In: Conrad K et al. (ed.) From pathogenesis to Therapy of Autoimmune Diseases: Autoantigens, Autoantibodies, Auroimmunity. 2009, Pabst Sci Publ.
[66]	Stoecker W, Otte M, Ulrich S et al. Antibodies against exocrine pancreas and goblet cells in the diagnostic of Crohn´s disease and ulcerative colitis. D. Med. Wschr 1984, 109: 1963-1969 (in German).
[67]	Davis MK., Andres JM., Jolley CD, Novak DA, Haafiz AB, González-Peralta RP. Antibodies to Escherichia coli outer membrane porin C in the absence of anti-Saccharomyces cerevisiae antibodies and anti-neutrophil cytoplasmic antibodies are an unreliable marker of Crohn´s disease and ulcerative colitis. J Pediatr Gastroenterol Nutr 2007; 45:409-413.
[68]	Ch’ng CL, Jones MK, Kingham JG. Celiac disease and autoimmune thyroid disease. Clin Med Res. 2007; 5:184-192.
[69]	Barker JM, Liu E. Celiac disease: pathophysiology, clinical manifestations, and associated autoimmune conditions. Adv Pediatr. 2008; 55:349-365.
[70]	Marietta EV, Camilleri MJ, Castro LA, Krause PK, Pittelkow MR, Murray JA. Transglutaminase autoantibodies in dermatitis herpetiformis and coeliac sprue. J. Invest. Dermatol. 128:332-335.
[71]	Turchin I, Barankin B (2005). "Dermatitis herpetiformis and gluten-free diet". Dermatology Online Journal 11: 6.
[72]	Van L, Browning JC, Krishnan RS, Kenner-Bell BM, Hsu S. Dermatitis herpetiformis: Potential for confusion with linear IgA bullous dermatosis on direct immunofluorescence. Dermatology Online Journal. 2008; 14: 21.
[73]	Desai L, Kurien RT, Simon EG, Dutta AK, Joseph AJ, Chowdhury SD. Hypogammaglobulinemia-associated gastrointestinal disease - a case series. Indian J Gastroenterol. 2014; 33:560-563.
[74]	Ardeniz Ö, Bașoğlu ÖK, Günșar F, Ünsel M, Bayraktaroğlu S et al. Clinical and Immunological Analysis of 23 Adult Patients With Common Variable Immunodeficiency. J Investig Allergol Clin Immunol 2010; 20:222-236.
[75]	Owen RG, Treon SP, Al-Katib A, et al. Clinicopathological definition of Waldenström’s macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenström’s Macroglobulinemia. Semin Oncol. 2003; 2: 110-115.
[76]	Sergej Konoplev, MD, PhD, L. Jeffrey Medeiros, MD, Carlos E. Bueso-Ramos, MD, PhD, Jeffrey L. Jorgensen, MD, PhD, and Pei Lin, MD. Immunophenotypic Profile of Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia. Am J Clin Pathol 2005; 124:414-420.
[77]	Waldmann TA, Steinfeld JL, Dutcher TF, Davidson JD, Gordon RS Jr. The role of the gastrointestinal system in "idiopathic hypoproteinemia". Gastroenterology 1961; 41: 197-207.
[78]	Freeman HJ. Small intestinal mucosal biopsy for investigation of diarrhea and malabsorption in adults. Gastrointest Endosc Clin N Am 2000; 10: 739-775.
[79]	Freeman HJ, Nimmo M Intestinal lymphangiectasia in adults. World J Gastrointest Oncol 2011 15; 3:19-23.
[80]	Perisic VN, Kokai G. Coeliac disease and lymphangiectasia. Arch Dis Child 1992; 67: 134-136.
[81]	Iida F, Wada R, Sato A, Yamada T. Clinicopathologic consideration of protein-losing enteropathy due to lymphangiectasia of the intestine. Surg Gynecol Obstet 1980, 151: 391-395.
[82]	Durand DV1, Lecomte C, Cathébras P, Rousset H, Godeau P Whipple disease. Clinical review of 52 cases. The SNFMI Research Group on Whipple Disease. Société Nationale Française de Médecine Interne. Medicine (Baltimore). 1997; 76:170-184.