**3. Nutrient deficiencies in CD**

Now a days, many patients with CD, may presents with no or minor gastrointestinal symptoms. The anemia including microcytic due to iron deficiency, macrocytic either due to vitamin B12 or folic acid deficiencies or even normocytic due to combined deficiencies is the initial manifestation of CD [16]. The possible explanation for high prevalence of nutritional deficiencies among CD patients include insufficient nutritional intake.

One of the commonest complications of CD is iron deficiency anemia; these patients may remain undiagnosed till their adult life [17]. The major cause of iron deficiency anemia includes decreased dietary intake, reduced absorption and blood loss. Among these causes, blood loss remained the most important one and it can be due to various sites including abdomen or urogenital. Reduced absorption of iron is an uncommon cause of iron deficiency, especially in healthy individuals and in resource rich countries. Iron is absorbed in the upper GI tract, and the duodenum is the site of maximum absorption [18]. There are multiple medical conditions which may lead to reduced absorption, and among them celiac is not an uncommon cause. The other conditions are atrophic gastritis, helicobacter pylori infection and bariatric surgery. Normal heme iron and normal gastric environment without acid reducing medications, facilitates absorption [19]. CD can contribute to anemia by several mechanisms, including iron deficiency by reduced absorption of supplemental iron and malabsorption of the other nutrients required for RBC production including B12, folic acid and copper [20]. There may also be a component of anemia of chronic disease and blood loss. Although the exact cause of blood loss in CD is unclear [21]. The causative pathology among these patients either includes mucosal abnormalities leading to oesophagitis and gastritis, or occult gastrointestinal bleeding [22]. The occult bleeding is due to excessive loss of intestinal cells and/or malabsorption of peroxidase-containing foods rather than loss of red blood cells [23]. Although the occult bleeding is not a common manifestation among patients with CD, thus occult bleeding is not a major contributing factor to iron deficiency anemia [24]. The classical presentation among these patients is recurrent iron deficiency with no recovery on supplemental therapy. The presentation of iron deficiency among these patients may include mild iron deficiency to severe heart failure.

The water soluble vitamins are B6 and folic acid which absorbed proximally and B12 which absorbed distally are the other commonly deficient vitamins [25]. The fat soluble vitamin A and D are also deficient in CD. Among these water and fat soluble vitamins, folic acid is the deficient most varying from 18 to 90% [26], followed by B12, vitamin A and D respectively. Overall vitamin deficiencies are barely seen in healthy individuals except for vitamin B12 which is commonly seen in healthy individuals [27]. The clinical presentation of folic acid includes mild cheilitis and sore mouth. Vitamin B12 and B6 deficient patients although presents with more severe manifestation including neurological symptoms.

**73**

*Complications of Celiac Disease*

mised as well [39].

cal manifestations.

**4. Neuropsychiatric complications of CD**

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

There is deficiency of other minerals including magnesium, copper, and zinc. Minerals form only 5% of the typical human diet but are essential for normal health and function. Although magnesium deficiency in humans is very unusual, it has been seen in individuals on a highly restricted diet or with celiac disease [28]. Magnesium is absorbed throughout the small intestine but the co-efficient is very low, possibly as low as 5% [29]. Its absorption decreases following high dietary intake or when total body magnesium is sufficient [30]. Due to deficiency patients may develop scaly dermatitis and dyslipidemia. Copper is the other mineral which may reduce in CD. It is absorbed in the proximal small intestine and stomach [31]. Though rare, acquired copper deficiency has been seen in humans. The common causes include fore gut surgery, premature infants, chronic malabsorptive conditions including CD and hemodialysis [32–34]. Copper deficiency may presents with fragile, abnormally-formed hairs, depigmentation of skin, muscle weakness and neurological abnormalities [35]. The neurological abnormalities are same as B12 deficiency. It may also causes anemia mimicking iron deficiency and neutropenia [36]. The other commonest deficient mineral is zinc. It is mainly absorbed in the duodenum and jejunum, and to a lesser extent in the ileum and large intestine [37]. In CD, the zinc deficiency may be due to increased endogenous losses of zinc, rather than abnormal zinc absorption. The clinical presentation of zinc deficiency includes wide array of skin lesions, growth retardation and hypogonadism [38]. The cell mediated immunity and antioxidants buffer capacity may be compro-

There is an established association of CD with different neuropsychiatric symptoms including headache, peripheral neuropathy, ataxia, depression, dysthymia, anxiety and epilepsy [40]. Peripheral neuropathies, characterized by burning, tingling, and numbness in hands and feet is quiet common among CD patients and sometimes the initial presentation as well. These neuropathies are associated with deficiencies of different vitamins including B1(thiamine), B2(riboflavin), B3(niacin), B6(pyridoxine), B12(cobalamin) and E, and mineral including copper. However, these deficiencies occurred when there is severe and extensive bowel involvement. Neuropathies may also be associated with lymphoma as well. Patients presenting with neurological manifestation has significant structural and functional brain deficits on MRI as compared to controls. The exact mechanism in relation to depression and epilepsy is not clear yet [41]. Patients with peripheral neuropathies do not responded on gluten free diet as compared to other neurologi-

**5. Metabolic bone disease and complications related to joints in CD**

The relationship of bone derangement and CD has been recognized since a long time, and can occur with or without gastrointestinal symptoms (**Table 2**). Low mineral density, reduced bone mass and increased fragility leading to increased risk of fracture is commonly seen in CD. These bone alteration are the consequence of impaired calcium and vitamin D absorption and secondary hyperparathyroidism, resulting primarily from the loss of villous cells in the proximal intestine, where calcium is mostly absorbed accounting for 90% of overall calcium absorption [42]. Minor amount of calcium is absorbed from stomach and intestine, the colon accounts for <10% of calcium absorption. Calcium absorption from intestine,

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

*Celiac Disease - From the Bench to the Clinic*

having ulcerative colitis alone [14].

**3. Nutrient deficiencies in CD**

include insufficient nutritional intake.

deficiency to severe heart failure.

severe manifestation including neurological symptoms.

diet.

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

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

Adult patients may rarely develop celiac crisis, presenting as profuse diarrhea

Now a days, many patients with CD, may presents with no or minor gastrointestinal symptoms. The anemia including microcytic due to iron deficiency, macrocytic either due to vitamin B12 or folic acid deficiencies or even normocytic due to combined deficiencies is the initial manifestation of CD [16]. The possible explanation for high prevalence of nutritional deficiencies among CD patients

One of the commonest complications of CD is iron deficiency anemia; these patients may remain undiagnosed till their adult life [17]. The major cause of iron deficiency anemia includes decreased dietary intake, reduced absorption and blood loss. Among these causes, blood loss remained the most important one and it can be due to various sites including abdomen or urogenital. Reduced absorption of iron is an uncommon cause of iron deficiency, especially in healthy individuals and in resource rich countries. Iron is absorbed in the upper GI tract, and the duodenum is the site of maximum absorption [18]. There are multiple medical conditions which may lead to reduced absorption, and among them celiac is not an uncommon cause. The other conditions are atrophic gastritis, helicobacter pylori infection and bariatric surgery. Normal heme iron and normal gastric environment without acid reducing medications, facilitates absorption [19]. CD can contribute to anemia by several mechanisms, including iron deficiency by reduced absorption of supplemental iron and malabsorption of the other nutrients required for RBC production including B12, folic acid and copper [20]. There may also be a component of anemia of chronic disease and blood loss. Although the exact cause of blood loss in CD is unclear [21]. The causative pathology among these patients either includes mucosal abnormalities leading to oesophagitis and gastritis, or occult gastrointestinal bleeding [22]. The occult bleeding is due to excessive loss of intestinal cells and/or malabsorption of peroxidase-containing foods rather than loss of red blood cells [23]. Although the occult bleeding is not a common manifestation among patients with CD, thus occult bleeding is not a major contributing factor to iron deficiency anemia [24]. The classical presentation among these patients is recurrent iron deficiency with no recovery on supplemental therapy. The presentation of iron deficiency among these patients may include mild iron

The water soluble vitamins are B6 and folic acid which absorbed proximally and B12 which absorbed distally are the other commonly deficient vitamins [25]. The fat soluble vitamin A and D are also deficient in CD. Among these water and fat soluble vitamins, folic acid is the deficient most varying from 18 to 90% [26], followed by B12, vitamin A and D respectively. Overall vitamin deficiencies are barely seen in healthy individuals except for vitamin B12 which is commonly seen in healthy individuals [27]. The clinical presentation of folic acid includes mild cheilitis and sore mouth. Vitamin B12 and B6 deficient patients although presents with more

and severe metabolic disturbances, if remained undiagnosed [15].

**72**

There is deficiency of other minerals including magnesium, copper, and zinc. Minerals form only 5% of the typical human diet but are essential for normal health and function. Although magnesium deficiency in humans is very unusual, it has been seen in individuals on a highly restricted diet or with celiac disease [28]. Magnesium is absorbed throughout the small intestine but the co-efficient is very low, possibly as low as 5% [29]. Its absorption decreases following high dietary intake or when total body magnesium is sufficient [30]. Due to deficiency patients may develop scaly dermatitis and dyslipidemia. Copper is the other mineral which may reduce in CD. It is absorbed in the proximal small intestine and stomach [31]. Though rare, acquired copper deficiency has been seen in humans. The common causes include fore gut surgery, premature infants, chronic malabsorptive conditions including CD and hemodialysis [32–34]. Copper deficiency may presents with fragile, abnormally-formed hairs, depigmentation of skin, muscle weakness and neurological abnormalities [35]. The neurological abnormalities are same as B12 deficiency. It may also causes anemia mimicking iron deficiency and neutropenia [36]. The other commonest deficient mineral is zinc. It is mainly absorbed in the duodenum and jejunum, and to a lesser extent in the ileum and large intestine [37]. In CD, the zinc deficiency may be due to increased endogenous losses of zinc, rather than abnormal zinc absorption. The clinical presentation of zinc deficiency includes wide array of skin lesions, growth retardation and hypogonadism [38]. The cell mediated immunity and antioxidants buffer capacity may be compromised as well [39].
