Advances in Clinical and Experimental Medicine
2017, vol. 26, nr 4, July, p. 729–737
doi: 10.17219/acem/62452
PubMed ID: 28691413
Publication type: review article
Language: English
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Diagnostic challenges in celiac disease
1 Department of Gastroenterology and Hepatology, Wroclaw Medical University, Poland
Abstract
Diagnosis of celiac disease in adults is currently based on serologic tests in combination with histopathological assessment of small intestinal biopsy specimens. High titers of celiac-specific antibodies in immunocompetent patients with villous atrophy in a good quality biopsy sample allow us to state a confident diagnosis. The relief of symptoms and histological improvement after embarking on a gluten free diet further support the initial diagnosis. However, in some cases, these conditions are not fulfilled, which requires a critical evaluation of laboratory and histopathology results and a consideration of other potential causes for the observed pathologies. To avoid diagnostic uncertainty, both biopsy and laboratory testing should be performed on a diet containing gluten. Immune deficiency, cross reaction of antibodies and possibilities of seronegative or latent celiac disease should be considered while evaluating serology results. Uneven distribution and variable intensity of histopathological changes in the small intestine along with multiple disorders presenting a similar specimen image may lead to invalid biopsy results. Additional laboratory testing and careful examination of a patient’s history may deliver important data for a differential diagnosis and a more specific biopsy evaluation. Persistence or recurrence of symptoms, despite the ongoing treatment, requires a revision of the initial diagnosis, an evaluation of the gluten free diet and a search for concurrent disorders or complications.
Key words
celiac disease, villous atrophy, lymphocytic duodenosis, non-celiac enteropathy, non-responsive celiac disease
References (45)
- Ludvigsson JF, Leffler DA, Bai JC, et al. The Oslo definitions for coeliac disease and related terms. Gut. 2013;62:43–52.
- Ludvigsson JF, Bai JC, Biagi F, et al. Diagnosis and management of adult coeliac disease: Guidelines from the British Society of Gastroenterology. Gut. 2014;63:1210–1228.
- Rubio–Tapia A, Hill ID, Kelly CP, Calderwood AH, Murray JA. American College of Gastroenterology clinical guidelines: Diagnosis and management of celiac disease. Am J Gastroenterol. 2013;108:656–676.
- Schyum AC, Rumessen JJ. Serological testing for celiac disease in adults. United European Gastroenterol J. 2013;1:319–325.
- Castillo NE, Theethira TG, Leffler DA. The present and the future in the diagnosis and management of celiac disease. Gastroenterol Rep. 2015;3:3–11.
- Hammer S, Greenson J. The Clinical Significance of Duodenal Lymphocytosis With Normal Villus Architecture. Arch Pathol Lab Med. 2013;137:1216–1219.
- Tursi A, Brandimarte G, Giorgetti GM. Prevalence of anti–tissue transglutaminase antibodies in different degrees of intestinal damage in celiac disease. J Clin Gastroenterol. 2003;36:219–221.
- Ierardi E, Losurdo G, Piscitelli D, et al. Seronegative celiac disease: Where is the specific setting? Gastroenterol Hepatol Bed Bench. 2015;8:110–116.
- Catassi C, Fasano A. Celiac disease diagnosis: Simple rules are better than complicated algorithms. Am J Gastroenterol. 2010;123:691–693.
- DeGaetani M, Tennyson CA, Lebwohl B, et al. Villous atrophy and negative celiac serology: A diagnostic and therapeutic dilemma. Am J Gastroenterol. 2013;108:647–653.
- Bao F, Green PH, Bhagat G. An update on celiac disease histopathology and the road ahead. Arch Pathol Lab Med. 2012;136:735–745.
- Serra S, Jani PA. An approach to duodenal biopsies. J Clin Pathol. 2006;59:1133–1150.
- Veress B, Franzén L, Bodin L, Borch K. Duodenal intraepithelial lymphocyte–count revisited. Scand J Gastroenterol. 2004;39:138–144.
- Evans KE, Aziz I, Cross SS, et al. A prospective study of duodenal bulb biopsy in newly diagnosed and established adult celiac disease. Am J Gastroenterol. 2011;106:1837–1742.
- Walker MM, Murray JA. An update in the diagnosis of coeliac disease. Histopathology. 2011;59:166–179.
- Aziz I, Evans KE, Hopper AD, Smillie DM, Sanders DS. A prospective study into theaetiology of lymphocytic duodenosis. Aliment Pharmacol Ther. 2010;32:1392–1397.
- Walker MM, Murray JA, Ronkainen J, et al. Detection of celiac disease and lymphocytic enteropathy by parallel serology and histopathology in a population–based study. Gastroenterology. 2010;139:112–119.
- Brown I, Mino–Kenudson M, Deshpande V, Lauwers G. Intraepithelial lymphocytosis in architecturally preserved proximal small intestinal mucosa: An increasing diagnostic problem with a wide differential diagnosis. Arch Pathol Lab Med. 2006;130:1020–1025.
- VandeVoort JL, Murray JA, Lahr BD, et al. Lymphocytic duodenosis and the spectrum of celiac disease. Am J Gastroenterol. 2009;104:142–148.
- Törnblom H, Lindberg G, Nyberg B, Veress B. Full–thickness biopsy of the jejunum reveals inflammation and enteric neuropathy in irritable bowel syndrome. Gastroenterology. 2002;123:1972–1979.
- Wahnschaffe U, Ullrich R, Riecken EO, Schulzke JD. Celiac disease–like abnormalities in a subgroup of patients with irritable bowel syndrome. Gastroenterology. 2001;121:1329–1338.
- Walker MM, Talley NJ, Prabhakar M, et al. Duodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis as possible disease markers in the irritable bowel syndrome and functional dyspepsia. Aliment Pharmacol Ther. 2009;29:765–773.
- Leffler D, Schuppan D, Pallav K, et al. Kinetics of the histological, serological and symptomatic responses to gluten challenge in adults with coeliac disease. Gut. 2013;62:996–1004.
- Catassi C, Bai JC, Bonaz B, et al. Non–Celiac Gluten Sensitivity: The New Frontier of Gluten Related Disorders. Nutrients. 2013;5:3839–3853.
- Sapone A, Bai JC, Ciacci C, et al. Spectrum of gluten–related disorders: consensus on new nomenclature and classification. BMC Medicine. 2012;10:13.
- Shidrawi RG, Przemioslo R, Davies DR, Tighe MR, Ciclitira PJ. Pitfalls in diagnosing coeliac disease. J Clin Pathology. 1994;47:693–694.
- Ludvigsson JF, Brandt L, Montgomery SM, Granath F, Ekbom A. Validation study of villous atrophy and small intestinal inflammation in Swedish biopsy registers. BMC Gastroenterology. 2009;9:19.
- Pallav K, Leffler DA, Tariq S, et al. Noncoeliacenteropathy: The differential diagnosis ofvillous atrophy in contemporary clinical practice. Aliment Pharmacol Ther. 2012;35:380–390.
- Hutchinson JM, West NP, Robins GG, Howdle PD. Long–term histological follow–up of people with coeliac disease in a UK teaching hospital. QJM. 2010;103:511–517.
- Rubio–Tapia A, Murray JA. Classification and management of refractory celiac disease. Gut. 2010;59:547–557.
- Woodward J. The management of refractory coeliac disease. Ther Adv Chronic Dis. 2013;4;77–90.
- Švajdler M, Daum O, Rychlý B: Diagnosing Celiac Disease: Role of the Pathologists. International Journal of Celiac Disease. 2014;2:70–75.
- Cyrany J, Vasatko, T, Machac J, Nova M, Szanyi J, Kopacova M. Telmisartan–associated enteropathy – is there any class effect? Aliment Pharmacol Ther. 2014; 40:569–570.
- Babbin BA, Crawford K, Sitaraman SV. Malabsorption work-up: Utility of small bowel biopsy. Clin Gastroenterol Hepatol. 2006;4:1193–1198.
- Nahon S, Patey-Mariaud De Serre N, et al. Duodenal intraepithelial lymphocytosis during Helicobacter pylori infection is reduced by antibiotic treatment. Histopathology. 2006;48:417–423.
- Oberhuber G, Stolte M. Giardiasis: Analysis of histological changes in biopsy specimens of 80 patients. J Clin Pathol. 1990;43:641–643.
- Gardner TB, Hill DR. Treatment of giardiasis. Clin Microbiol Rev. 2001;14:114–128.
- Greenson JK. The biopsy pathology of non-coeliac enteropathy. Histopathology. 2015;66:29–36.
- Muir-Padilla J, Myers J. Whipple disease: A Case report and review of the literature. Arch Pathol Lab Med. 2005;129: 933–936.
- Teahon K, Webster AD, Price AB, Weston J, Bjarnason I. Studies on the enteropathy associated with primary hypogammaglobulinaemia. Gut. 1994;35:1244–1249.
- Ameratunga R, Woon ST, Gillis D, Koopmans W, Steele R. New diagnostic criteriafor common variable immune deficiency (CVID), which may assist with decisions to treat with intravenous or subcutaneous immunoglobulin. Clin Exp Immunol. 2013;174:203–211.
- Biagi F, Bianchi PI, Zilli A, et al. The significance of duodenal mucosal atrophy inpatients with common variable immunodeficiency: A clinical and histopathologic study. Am J Clin Pathol. 2012;138:185–189.
- Halfdanarson TR, Litzow MR, Murray JA. Hematologic manifestations of celiac disease. Blood. 2007;109:412–421.
- Al-Saleem T, Al-Mondhiry H. Immunoproliferative small intestinal disease(IPSID): A model for mature B-cell neoplasms. Blood. 2005;105:2274–2280.
- Freeman HJ. Update on collagenous sprue. World J Gastroenterol. 2010;16:296–298.