History and exam

Key diagnostic factors

immunoglobulin (IgA) deficiency

Multiple studies have shown an association between IgA deficiency and celiac disease. Although the pathogenesis is unclear, it has been proposed that a lack of secretory IgA and Peyer patch malfunction allow for increased free gluten peptides in the submucosa. [18]

diarrhea

Patients with longstanding or refractory abdominal symptoms should be screened for celiac disease. [34] Patients may present with chronic or intermittent diarrhea.

bloating

Patients with longstanding or refractory abdominal symptoms should be screened for celiac disease. [34]

abdominal pain/discomfort

Patients with longstanding or refractory abdominal symptoms should be screened for celiac disease. [34] Patients may present with recurrent abdominal pain, cramping, or distension. [41]

anemia

Iron deficiency anemia is the most common clinical presentation in adults. Folate (and rarely vitamin B12) deficiency may lead to a macrocytic anemia. [42]

dermatitis herpetiformis

Characterized by intensely pruritic papulovesicular lesions that occur symmetrically over the extensor surfaces of the arms and legs, as well as on the buttocks, trunk, neck, and scalp. [42] Biopsy-proven dermatitis herpetiformis almost universally occurs in association with celiac disease.

Other diagnostic factors

family history

Family history of celiac disease or other autoimmune disorders.

osteopenia/osteoporosis

History of bone pain or previous fracture, due to vitamin D deficiency and hypocalcemia.

fatigue

Associated with iron deficiency anemia. [42]

weight loss

Likely multifactorial, primarily due to malabsorption but also to changes in motility, metabolism, and appetite. [42]

failure to thrive

In children, faltering growth and delayed puberty are indications for testing for celiac disease. [48]

type 1 diabetes

Clinicians caring for patients with type 1 diabetes mellitus should be aware of the association with celiac disease and consider testing if there are any digestive symptoms or laboratory changes to suggest celiac disease. [43]  Some clinicians suggest screening asymptomatic individuals with type 1 diabetes mellitus for celiac disease every 5 years but the clinical benefits of this approach are not well established. [44]  

autoimmune thyroid disease

Clinicians caring for patients with autoimmune thyroid disease should be aware of the association with celiac disease and consider testing if symptoms occur. [24] [43] Unexplained increasing need for levothyroxine or treatment-refractory hypothyroidism should also lead to celiac disease testing. [45] [46]  Correspondingly, patients with celiac disease should be screened for thyroid disease. [47]

aphthous stomatitis

Caused by various nutritional deficiencies, although the particular deficiency is not always evident. [49] May be recurrent.

dental enamel hypoplasia

The exact etiology is unclear but is felt to be due to nutritionally derived abnormalities in mineralization.

easy bruising

Vitamin K deficiency may lead to a coagulopathy.

peripheral neuropathy

The etiology of neurologic dysfunction may be the result of either vitamin deficiencies (B12, E, or D; folate or pyridoxine) or autoimmune activity against neural antigens. [49]

ataxia

Cerebellar ataxia is one of the more common neurologic symptoms. [49]

Risk factors

family history of celiac disease

Multiple studies have shown an increased risk in family members, likely secondary to genetic factors. [17]

immunoglobulin A deficiency

Multiple studies have shown an association between immunoglobulin A (IgA) deficiency and celiac disease. Although the pathogenesis is unclear, it has been proposed that a lack of secretory IgA and Peyer patch malfunction allow for increased free gluten peptides in the submucosa. [18]

type 1 diabetes

The association between type 1 diabetes mellitus and celiac disease is well known. It is probably based on genetic factors favoring autoimmunity, including the presence of human leukocyte antigen (HLA)-DQ2 and HLA-DQ8 and single nucleotide polymorphisms shared by both diseases. [19] [20]  Leaky gut, with tight junction defects leading to increased passage of luminal peptides into the submucosa, resulting in immune activation, is also hypothesized, as well as enhanced basal expression of inflammatory markers. [21] [22]

autoimmune thyroid disease

Multiple studies have shown an association between thyroid disease and celiac disease. Pathogenesis is similar to that of type 1 diabetes mellitus. [23] Celiac disease may be more prevalent in individuals with hyperthyroidism than those with hypothyroidism. [24]

Down syndrome

Many studies show an association between Down syndrome and celiac disease, although one study refutes this. The mechanism is unclear because celiac disease does not appear to be linked to genes found on chromosome 21. [25] [26]

Sjogren syndrome

Some studies have shown an increased prevalence of celiac disease in patients with Sjogren syndrome. [27]

inflammatory bowel disease

A few studies have shown an increased prevalence of celiac disease in patients with Crohn disease and, to a lesser extent, ulcerative colitis. [28]

primary biliary cirrhosis

Studies have shown an increased prevalence of celiac auto-antibodies in patients with primary biliary cirrhosis and other liver diseases, but false positives appear higher in these populations. [29]

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