**1. Introduction**

Celiac disease (CD) is one of the commonest malabsorptive syndromes, of either one or more nutrients. It was historically known as a disease of whites, but in recent era, it is as commonly seen in other parts of the world, including Asian and African countries [1, 2]. Because of its various categories starting from full blown CD, to completely asymptomatic variety, the clinical presentation dispersed among individuals. Although the commonest presentation is the gastrointestinal manifestation but many individuals may present with malignancies associated with CD. The logical answer for this diverse and late manifestation may be due to prolonged breast feeding and late commencement of gluten diet among infants, which was the usual presenting age among infants [3]. The usual age of presentation of CD now is 10–40 years [4].

In recent days, young patients still presenting with classical symptoms of CD, i.e. gastrointestinal, although may have complications at the time of initial presentation. The older individuals usually present with complications of different varieties, which make CD to diagnose late [5] (**Table 1**).

Among different categories of CD, including classical CD, atypical CD, asymptomatic and latent CD the presentation are different and thus complications.

Classical celiac disease: The classical one, including three features: villous atrophy, symptoms of malabsorption and resolution of symptoms with gluten free diet.


#### **Table 1.**

*Complications of celiac disease.*

This variant presents with malabsorption with vitamin and nutrient deficiencies. The malabsorptive symptoms include steatorrhea, weight loss, abdominal pain and diarrhea [6]. These patients also developed muscle weakness, muscle and bone pain, tooth enamel defect and lactase malabsorption [7]. These patients have various kind of nutrient and mineral deficiency including iron, folic acid, vitamin B12, vitamin D and zinc mostly, although they may have deficiency of other minerals as well.

Non-classical and atypical CD: The non-classical CD patients may have both gastrointestinal symptoms as in classical one, or they present with other associated manifestations of CD, including dermatitis herpetiformis, IgA deficiency, type 1 diabetes mellitus, autoimmune thyroid illness, enamel defects and infertility. These patients also have severe mucosal damage and having specific celiac antibody pattern.

The asymptomatic or silent CD: This variant remained undiagnosed, or incidentally diagnosed upon screening. They usually do not have any symptomatology except a little fatigue, which occurs after introduction of gluten free diet. Although these patients have classical architectural remodeling of intestinal mucosa as in classical CD, i.e. crypt hyperplasia and villous atrophy, but do not developed gastric symptoms; neither had they developed complications related to CD.

Latent CD: There are some patients among CD who have minor or no symptoms with normal jejunal mucosa, and remained asymptomatic if on gluten free diet. In this variant only 20% remained asymptomatic till adulthood and do not develop any complication of CD and having normal architecture throughout. The rest of the patients developed various degree of villous atrophy [8] and thus may develop complications related to CD. These patients may develop malabsorption with multiple nutrient deficiencies and lymphoma.

Refractory CD: It is defined as persistent or recurrent symptoms typically diarrhea and weight loss with signs of malabsorption .despite on strict gluten free diet. It is accompanied by villous atrophy. Both the variants of refractory CD is associated with increased risk of lymphoma [9].

## **2. Gastrointestinal complications of CD**

The classical CD may present with complications related to gastrointestinal symptomatology including recurrent foul smelling, bulky loose stools, and due to steatorrhea and flatulence. The mechanism of developing steatorrhea is primarily due to changes in jejunal mucosal function. Due to changes in jejunal brush border enzymatic function; these patients may develop secondary lactase deficiency, leading to diarrhea even after ingestion of milk and milk products, which further

**71**

**Figure 2.**

*Villous atrophy in CD.*

**Figure 1.**

*Complications of Celiac Disease*

evaluated for CD [12].

*DOI: http://dx.doi.org/10.5772/intechopen.80465*

endogenous fluid secretion (**Figures 1** and **2**).

irritable bowel syndrome type symptoms.

increases the development of complications [10]. In cases of extensive involvement of ileum, patients with CD may complicate with bile acid malabsorption resulting in bile acid induced fluid secretin in the colon. Crypt hyperplasia may lead to

CD presenting in early age may complicate with short stature or stunted growth due to deficiency of multiple nutrients and minerals. These patients may also have severe weight loss, anemia of different types, and osteopenia. Due to shifting of classical symptoms to asymptomatic variety, patients with CD, may presents with

An association of CD is seen with gastroesophageal reflux disease, and it is much higher in CD than controls. These patients usually responded on gluten free diet within 3 months' time [11]. Eosinophilic esophagitis is another common complication among patients with CD. Patients with persistent reflux or dysphagia should be

Because same pro-inflammatory polymorphism of the IL-23, receptor in both ulcerative colitis and CD, they may co-exist. The incidence of ulcerative colitis is

*Comparison of blunting and flattening of villi with normal mucosa (left) in CD.*

## *Complications of Celiac Disease DOI: http://dx.doi.org/10.5772/intechopen.80465*

*Celiac Disease - From the Bench to the Clinic*

This variant presents with malabsorption with vitamin and nutrient deficiencies. The malabsorptive symptoms include steatorrhea, weight loss, abdominal pain and diarrhea [6]. These patients also developed muscle weakness, muscle and bone pain, tooth enamel defect and lactase malabsorption [7]. These patients have various kind of nutrient and mineral deficiency including iron, folic acid, vitamin B12, vitamin D and zinc mostly, although they may have deficiency of other minerals as well. Non-classical and atypical CD: The non-classical CD patients may have both gastrointestinal symptoms as in classical one, or they present with other associated manifestations of CD, including dermatitis herpetiformis, IgA deficiency, type 1 diabetes mellitus, autoimmune thyroid illness, enamel defects and infertility. These patients also have severe mucosal damage and having specific celiac antibody

Infertility

Glomerular IgA nephropathy

Cardiomyopathy/myocarditis

**Gastrointestinal complications Non-gastrointestinal complications** Malabsorption Nutrient and mineral deficiencies Intestinal lymphomas Osteoporosis/osteomalacia

Other GI malignancies Idiopathic pulmonary hemosiderosis

Collagenous sprue Dental defects

The asymptomatic or silent CD: This variant remained undiagnosed, or incidentally diagnosed upon screening. They usually do not have any symptomatology except a little fatigue, which occurs after introduction of gluten free diet. Although these patients have classical architectural remodeling of intestinal mucosa as in classical CD, i.e. crypt hyperplasia and villous atrophy, but do not developed gastric

Latent CD: There are some patients among CD who have minor or no symptoms with normal jejunal mucosa, and remained asymptomatic if on gluten free diet. In this variant only 20% remained asymptomatic till adulthood and do not develop any complication of CD and having normal architecture throughout. The rest of the patients developed various degree of villous atrophy [8] and thus may develop complications related to CD. These patients may develop malabsorption with multiple

Refractory CD: It is defined as persistent or recurrent symptoms typically diarrhea and weight loss with signs of malabsorption .despite on strict gluten free diet. It is accompanied by villous atrophy. Both the variants of refractory CD is associ-

The classical CD may present with complications related to gastrointestinal symptomatology including recurrent foul smelling, bulky loose stools, and due to steatorrhea and flatulence. The mechanism of developing steatorrhea is primarily due to changes in jejunal mucosal function. Due to changes in jejunal brush border enzymatic function; these patients may develop secondary lactase deficiency, leading to diarrhea even after ingestion of milk and milk products, which further

symptoms; neither had they developed complications related to CD.

nutrient deficiencies and lymphoma.

ated with increased risk of lymphoma [9].

**2. Gastrointestinal complications of CD**

**70**

pattern.

**Table 1.**

*Complications of celiac disease.*

increases the development of complications [10]. In cases of extensive involvement of ileum, patients with CD may complicate with bile acid malabsorption resulting in bile acid induced fluid secretin in the colon. Crypt hyperplasia may lead to endogenous fluid secretion (**Figures 1** and **2**).

CD presenting in early age may complicate with short stature or stunted growth due to deficiency of multiple nutrients and minerals. These patients may also have severe weight loss, anemia of different types, and osteopenia. Due to shifting of classical symptoms to asymptomatic variety, patients with CD, may presents with irritable bowel syndrome type symptoms.

An association of CD is seen with gastroesophageal reflux disease, and it is much higher in CD than controls. These patients usually responded on gluten free diet within 3 months' time [11]. Eosinophilic esophagitis is another common complication among patients with CD. Patients with persistent reflux or dysphagia should be evaluated for CD [12].

Because same pro-inflammatory polymorphism of the IL-23, receptor in both ulcerative colitis and CD, they may co-exist. The incidence of ulcerative colitis is

#### **Figure 1.**

*Comparison of blunting and flattening of villi with normal mucosa (left) in CD.*

**Figure 2.** *Villous atrophy in CD.*

much higher than Crohn's disease in patients with CD [13]. Patients having both CD and ulcerative colitis have more chances to have pancolitis as compared to patients having ulcerative colitis alone [14].

Oral lesions including erythema or atrophy, and soreness or burning sensation of the tongue have been associated with CD and can be resolved with gluten free diet.

Adult patients may rarely develop celiac crisis, presenting as profuse diarrhea and severe metabolic disturbances, if remained undiagnosed [15].
