Celiac disease

Celiac disease, also known as non-tropical sprue, is the most common gluten-related disorder and is a T-cell mediated autoimmune chronic gluten intolerance condition characterized by a loss of villi in the proximal small bowel and gastrointestinal malabsorption (sprue).

It should always be considered as a possible underlying etiology in cases of iron deficiency anemia of uncertain cause.

Epidemiology

Celiac disease is relatively common in the White population, 1 in 200, but it is extremely rare in the Asian and Black population. There are two peaks of presentation, a small number of patients present early in childhood and the second, larger group of patients present in the 3^rd and 4^th decades. 

Associations

• idiopathic pulmonary hemosiderosis: as part of Lane-Hamilton syndrome ⁴

• dermatitis herpetiformis

• IgA deficiency

• cavitating mesenteric lymph node syndrome ¹⁴

• small bowel lymphoma, in particular, enteropathy-associated T cell lymphoma, but also other non-Hodgkin lymphomas ¹¹

• Down syndrome (trisomy 21) ¹²

• CEC syndrome (Gobbi syndrome): celiac disease, epilepsy and cerebral calcification ¹³

• inflammatory bowel disease ^21,22

  • Crohn disease 7-10x risk

  • ulcerative colitis 4-7x risk

Clinical presentation

Many patients have a paucity of symptoms with no gastrointestinal upset. However, abdominal pain is considered the most common symptom. Other manifestations include:

• iron-deficiency anemia and guaiac-positive stools

• abnormal bowel habit (e.g. diarrhea and/or constipation)

• malabsorption, including fat-soluble vitamins

• weight loss

In addition to gastrointestinal manifestations, some individuals may have other systemic manifestations, sometimes without evidence of enteropathy. These include ^16,17: 

• central nervous system manifestations of celiac disease

  • gluten ataxia

  • peripheral neuropathy

• dental manifestations of celiac disease

  • enamel defects

• endocrinological manifestations of celiac disease

  • delayed puberty

  • infertility and subfertility

  • autoimmune thyroid disease is more common in individuals with celiac disease

• hematological manifestations of celiac disease

  • anemia (common in poorly treated individuals)

• hepatobiliary manifestations of celiac disease

  • hypertransaminasemia

  • usually mild but rarely can lead to liver failure

• musculoskeletal manifestations of celiac disease

  • poor growth

  • rickets (rare when celiac disease is recognized and treated)

  • osteoporosis (common in elderly)

  • myopathy

Pathology

Celiac disease is a chronic autoimmune disease induced in genetically susceptible individuals after ingestion of gluten. Small bowel mucosa is primarily affected (submucosa, muscularis and serosa remain unaffected), resulting in progressive degrees of villous inflammation and destruction. The disease tends to start in the duodenum and extends into the ileum, resulting in induction crypt hyperplasia. There is loss of villi, which absorb fluid, and hypertrophy of crypts, which produce fluid, resulting in excess fluid in the small bowel lumen ⁸.  

The villous atrophy that occurs within the bowel also results in malabsorption of iron, folic acid, calcium and fat-soluble vitamins manifesting in a variety of signs, some of which may be non-specific.

The gold standard diagnostic test is a duodenal biopsy taken at endoscopy.

Microscopic appearance

• total villous loss, initially blunting, progressing to flattened mucosa

• hyperplasia of the crypts 

• epithelial infiltration with T-cell lymphocytes

Markers

Additionally, serum antibodies may be raised:

• antitissue transglutaminase antibody (anti-tTG), IgA

• deamidated gliadin peptide (DGP) antibodies, IgA

• antiendomysial antibodies (EMA), IgA class

• antireticulin antibodies (ARA), IgA class

Quantitative immunoglobulin A (IgA): measures the total level of IgA in the blood to determine if someone is deficient in the IgA class of antibodies. The IgG class of anti-tTG may be assayed for people who have a deficiency of IgA.

Radiographic features

Fluoroscopy

Features of small bowel barium studies are not sensitive enough for confident diagnosis, but the following changes may be seen:

• small intestinal dilatation due to excess fluid

• dilution of contrast

• multiple non-obstructing intussusceptions (coiled spring appearance)

• jejunoileal fold pattern reversal

• moulage sign

• mosaic pattern

• flocculation

• segmentation

CT/MRI

Features present on CT enteroclysis and MR enterography may include ^3,6,18-20:

• jejunoileal fold pattern reversal: thought to have the highest specificity is considered the most discriminating independent variable for the diagnosis of uncomplicated celiac disease

• ileal fold thickening

• small bowel dilatation

• perienteric stranding

• intussusceptions

• strictures

• vascular engorgement

• prominent mesenteric lymph nodes may cavitate with a fluid-fat level

• lymphadenopathy

• submucosal fat deposition in long-standing cases

• other adjunctive features

  • splenic atrophy

Treatment and prognosis

A strict lifelong gluten-free diet is the mainstay of treatment of this condition and is effective in the vast majority of patients.

A small subset of patients do not respond despite fastidious gluten-free nutrition, representing refractory celiac disease ¹⁵.

Complications

• increased risk of malignant conditions such as small bowel lymphoma (mainly T-cell type) and small bowel adenocarcinoma

• ulcerative jejunoileitis ¹

• increased risk of development of carcinoma of the esophagus

• cavitating lymph node syndrome ^1,2

  • hyposplenism ¹