Small intestine & ampulla
Malabsorption
Celiac sprue
Author: Erdener Özer, M.D., Ph.D.
Topic Completed: 1 June 2017
Minor changes: 18 November 2020
Copyright: 2002-2021, PathologyOutlines.com, Inc.
PubMed Search: Celiac sprue[TI] small bowel
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Pathophysiology | Etiology | Diagrams / tables | Clinical features | Diagnosis | Laboratory | Prognostic factors | Case reports | Treatment | Clinical images | Microscopic (histologic) description | Microscopic (histologic) images | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1Cite this page: Özer E. Celiac sprue. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/smallbowelceliacsprue.html. Accessed January 15th, 2021.
Definition / general
- Chronic inflammatory disorder of the small intestine characterized by malabsorption after ingestion of gluten in individuals with a certain genetic background
- Major cause of malabsorption
Essential features
- Increased numbers of lymphocytes infiltrate the epithelium (intraepithelial lymphocytosis)
- Partial or total atrophy of intestinal villi and hyperplasia of intestinal crypts with chronic inflammation in the lamina propria
Terminology
- Celiac disease
- Nontropical sprue
- Gluten sensitive enteropathy
- Gluten induced enteropathy
ICD coding
Epidemiology
- Incidence of 0.3 - 1.2% in Europe, North America and Australia (Dig Liver Dis 2011;43:S385)
- All ages with a preference for females (male/female ratio 1:2) (Dig Liver Dis 2011;43:S385)
Pathophysiology
- Damage to the intestinal mucosa occurs with the presentation of gluten derived peptide gliadin by HLA molecules to helper T cells, which mediate the inflammatory response, causing epithelial damage
- Destruction of the intestinal absorptive surface leads to malabsorption
Etiology
- Celiac disease results from a combination of immunological responses to an environmental factor (gliadin) and genetic factors (Dig Liver Dis 2011;43:S385)
- It has a strong hereditary component; the prevalence of the condition in first degree relatives is approximately 10% (Dig Liver Dis 2011;43:S385)
- Strong association exists between celiac disease and HLA haplotypes DQ2 and DQ8 (Dig Liver Dis 2011;43:S385)
Diagrams / tables
Modified Marsh-Oberhuber classification of histologic findings in celiac disease:
| Marsh type |
IEL/100 enterocytes - jejunum |
IEL/100 enterocytes - duodenum |
Crypt hyperplasia |
Villi |
| 0 | < 40 | < 30 | Normal | Normal |
| 1 | > 40 | > 30 | Normal | Normal |
| 2 | > 40 | > 30 | Increased | Normal |
| 3a | > 40 | > 30 | Increased | Mild atrophy |
| 3b | > 40 | > 30 | Increased | Marked atrophy |
| 3c | > 40 | > 30 | Increased | Complete atrophy |
Images hosted on other servers:
Comparison of
four classification
schemes
Diagnostic approach of refractory disease
Clinical features
- Variety of clinical manifestations complicates its recognition:
- Malabsorption syndrome with repeated diarrhea-like bowel movements, abdominal pain and marked weight loss
- Dermatitis herpetiformis
- Endoscopy may show scalloping or flattening of duodenal folds, fissuring over the folds and a mosaic pattern of mucosa of folds
- Refractory (unclassified sprue): celiac sprue that does not respond to gluten free diet of 6 - 12 months
- Note: must rule out diet with gluten contamination, microscopic colitis, bacterial overgrowth, pancreatic insufficiency, lactose intolerance, inflammatory bowel disease, lymphoma (Gut 2010;59:547)
- Two subtypes: type 1 (normal intraepithelial lymphocyte phenotype) and type 2 (presence of abnormal clonal intraepithelial lymphocyte phenotype)
- Often associated with thromboembolic events, coexisting autoimmune disorders, cavitation of mesenteric lymph nodes and hyposplenism, lymphoma
Diagnosis
- Correct diagnosis requires precise evaluation of clinical, serological, genetic and histological aspects
- Laboratory tests include elevated IgA class antitransglutaminase antibodies (tTGA), IgA class antiendomysial antibodies (EMA) and IgA class antigliadin antibodies (AGA)
- Individuals with seronegative disease may show histologic changes
- Intestinal biopsies from the first and second duodenal portion are essential to confirm the diagnosis
- Genetic testing for histocompatibility antigens (HLA) is never diagnostically significant
Laboratory
- tTGA has the highest sensitivity for celiac disease (98%) specificity is 90% (Arch Pathol Lab Med 2012;136:735)
- EMA, while having a lower sensitivity, shows an almost absolute specificity (Arch Pathol Lab Med 2012;136:735)
- IgA class antigliadin antibodies (AGA) is now an obsolete test (Arch Pathol Lab Med 2012;136:735)
Prognostic factors
- Prognosis for patients with correctly diagnosed and treated celiac disease is excellent
- Complications that can be confirmed histologically:
- Refractory sprue
- Collagenous sprue
- Ulcerative jejunoileitis
- Lymphoma
- Have increased risk for malignancy, including enteropathy associated T cell lymphoma and adenocarcinoma of the intestinal tract
Case reports
- Toddler with atypical onset for celiac disease (Med Ultrason 2016;18:116)
- 2 year old girl with chronic diarrhea (Eur J Gastroenterol Hepatol 2014;26:679)
- 20 year old woman with dermatitis herpetiformes (Cases J 2009;2:7512)
- 41 year old man with classic symptoms (Postgrad Med 2009;121:166)
- 46 year old woman with celiac disease, previously diagnosed with seronegative arthritis and inflammatory bowel disease (Cases J 2009;2:9330)
Treatment
- Primary management of celiac disease is dietary
- Complete elimination of gluten containing grain products (including wheat, rye and barley) is essential to treatment
Clinical images
Contributed by Erdener Özer, M.D., Ph.D.
Normal versus flattened mucosa
Microscopic (histologic) description
- Histological "elementary lesions" are (Dig Liver Dis 2011;43:S385, Semin Diagn Pathol 2014;31:124):
- Increased intraepithelial T lymphocytes (IEL): 25 to 29 IEL/100 enterocytes is considered borderline; > 30 IEL/100 enterocytes represents a pathological "lymphocytosis"
- Decreased enterocyte height, flattening of enterocytes, intracytoplasmic vacuolation and reduction or absence of brush border are suggestive but not specific
- Crypt hyperplasia: extension of the regenerative epithelial crypts associated with changes in the presence of more than 1 mitosis per crypt
- Villous atrophy: decrease in villous height, alteration of normal crypt/villous ratio (3:1) until total disappearance of villi; this assessment requires proper orientation of the biopsies
- Diagnostic categories are based on these elementary lesions:
- Modified Marsh-Oberhuber classification of histologic findings in celiac disease
- Simplified systems (Corazza & Villanaci or Ensari), which may be more reproducible (Arch Pathol Lab Med 2010;134:826, Pathol Res Pract 2016;212:1174)
- Different grades of duodenal mucosal lesions:
- Grade A / type 1: increased intraepithelial lymphocytes but no villous atrophy
- Grade B1 / type 2: villi still present but shortened
- Grade B2 / type 3: complete villous atrophy
Microscopic (histologic) images
Contributed by Erdener Özer, M.D., Ph.D.
Normal versus Marsh type IIIb / IIIC
Contributed by Arzu Ensari, M.D., Ph.D.
Response to gluten free diet; collagenous sprue
Case #127
56 year old woman
Differential diagnosis
- Many disorders nave similar architectural abnormalities or intraepithelial lymphocytosis but those most likely encountered by pathologists are:
- Autoimmune enteropathy: histologic findings of villous flattening and crypt hyperplasia are similar to celiac disease
- Crohn's disease
- Chronic H. pylori associated duodenitis: Helicobacter pylori gastritis can cause an increase in IELs in the duodenal bulb, leading to diagnostic confusion with celiac disease
- Food allergy: hypersensitivity to food antigens other than gluten, including cow's milk, soy protein, fish, rice and chicken may also be associated with increased numbers of IELs, as well as architectural changes in the form of patchy or diffuse disease
- Infections: a wide variety of infectious agents including viruses, parasites and bacteria can affect small intestinal mucosa
Additional references
Board review style question #1
Which histological feature is most common in celiac disease?
- Crypt hyperplasia
- Granulomas
- Intraepithelial lymphocytosis
- Mucosal eosinophilia
- Villous atrophy
Board review style answer #1
C. Intraepithelial lymphocytosis. All celiac disease patients except for those with Marsh type 0 show
intraepithelial lymphocytosis.
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