Celiac Disease

Symptoms of Celiac Disease

Celiac disease (CD) can present with many symptoms, ranging from typical gastrointestinal manifestations to only atypical signs (tabel 1) or no symptoms at all. About 50% of patients with CD present with atypical symptoms. Therefore, in many cases, especially among adults, CD remains undiagnosed.

Tabel 1. Clinical manifestations of celiac disease (Tack GJ, 2010, Megiorni F, 2012)

Typical signs and symptoms Atypical signs and symptoms Associated diseases
 Abdominal distension Alopecia areata Addison disease
 Abdominal pain Anemia Atrophic gastritis
Anorexia Aphthous stomatitis Autoimmune hepatitis
Bulky, sticky and pale stools Arthritis Autoimmune pituitaritis
Diarrhea Attention-deficit hyperactivity disorder Autoimmune thyroiditis
Flatulence Cerebellar ataxia Behçet disease
Failure to thrive Chronic fatigue, weakness Dermatomyositis
Muscle wasting Constipation Inflammatory arthritis
Nausea Dental anomalies Multiple sclerosis
Steatorrhea Depression Myasthenia gravis
Vomiting Dermatitis herpetiformis Primary biliary cirrhosis
Weight loss Epilepsy Primary sclerosing cholangitis
Esophageal reflux Psoriasis
Hepatic steatosis Sjögren disease
Infertility, miscarriage Type 1 diabetes mellitus
Isolated hypertransaminasemia Vitiligo
Late-onset puberty
Mouth ulcers
Osteoporosis, osteopenia
Peripheral neuropathy
Recurrent abdominal pain
Short stature


Although CD has long been considered a pediatric syndrome, it has also been increasingly diagnosed in older children and adults. Clinical manifestation of CD is influenced by age of onset, gender (the ratio of female to male is 2:1), extent of mucosal injury and dietary habits.

In addition, gluten intolerance is more frequent in risk groups, such as first-degree relatives of patients (up to 20% in siblings) as well as individuals with specific genetic syndromes like Down syndrome (5-10%), Turner syndrome (~7%) and Williams syndrome (9.5%) or autoimmune diseases like type 1 diabetes (4%-19%), thyroiditis (2%-5%) and multiple sclerosis (~10%) suggesting the existence of common predisposing genes to autoimmunity.


CD is usually detected by serologic testing of celiac-specific antibodies and confirmed by duodenal mucosal biopsies. Both serology and biopsy should be performed on a gluten- rich diet. Anti-tissue transglutaminase (TTG) antibody, deamidated gliadin peptide (DGP) antibody and endomysium antibody (EMA) based assays are the preferred initial tests for detection of disease. A positive serological test is supportive of the diagnosis but no single test is 100% specific for CD and the diagnostic accuracy varies a lot between laboratories. If the suspicion for CD is high, intestinal biopsy should be carried out even when serologies are negative. The confirmation of CD diagnosis should be based on a combination of findings from the medical history, physical examination, serology, and upper endoscopy with histological analysis of multiple biopsies of the duodenum.

A recent guideline published by the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) proposed that any intestinal biopsy in children could be avoided if the following criteria are met: characteristic symptoms of CD, TTG IgA levels >10× upper limit of normal (confirmed with a positive EMA in a different blood sample), and positive HLA-DQ2.

Testing for human leukocyte antigen (HLA)-DQ genes and confirmatory serology allow reducing the numbers of unnecessary gastroscopies. HLA-DQ2/DQ8 genotyping should be used to exclude CD if the individual with CD symptoms has discordant or negative serologic and histologic findings. HLA-DQ2 (~95%) or HLA-DQ8 (~5%) is present in almost all patients with CD. Negative results for both HLA- DQ types make a CD diagnosis highly unlikely (negative predictive value is >99%). Among rare CD patients who do not carry either HLA-DQ2 or HLA-DQ8 heterodimers, majority still carried one-half of the HLA-DQ2 heterodimer.

HLA-DQ2/DQ8 haplotypes are present in approximately 30–40% of Caucasian population and only a fraction (up to 3%) of these individuals have CD. Therefore, testing for CD with either HLA-DQ type is not useful because the positive predictive value is only ~12%. HLA-DQ2/DQ8 testing should not be used routinely in the initial diagnosis of CD, but rather should be used to effectively rule out the disease in specific clinical situations in patients at increased risk of CD. For example:

  • equivocal small-bowel histological finding in seronegative patients;
  • evaluation of patients on a gluten free diet (GFD) in whom no testing for CD was done before GFD;
  • patients with discrepant celiac-specific serology and histology;
  • screening of at-risk groups (e. g. first-degree relatives, specific syndromes and diseases)


Strict, lifelong gluten free diet (GFD) is currently the only effective treatment for CD as no medication exists that can reliably prevent gluten caused damage to the mucosa of the small intestine. Early diagnosis of CD is important for starting a therapeutic diet as soon as possible, because untreated CD significantly increases risk of developing long- term complications such as malnutrition, malignancy, osteoporosis, infertility, and autoimmunity. The diet requires complete elimination of all forms of wheat, barley, rye and their derivatives. However, in reality this is hardly achievable due to contamination of foods with trace amounts of gluten. Although there is no evidence to suggest a single definitive threshold, according to a systematic review published in 2008, gluten intake of <10 mg per day is unlikely to cause damage in most patients (Akobeng AK and Thomas AG, 2008). The current international Codex Alimentarius defines gluten-free foods as having up to 20 ppm (20mg/kg) of gluten. After introduction of uncontaminated oats into the diet of people with CD there should be careful follow-up to detect appearance of any signs of both clinical and serological relapse.

Recommendations by American College of Gastroenterology guidelines on CD

  1. Patients with symptoms, signs, or laboratory evidence suggestive of malabsorption, such as chronic diarrhea with weight loss, steatorrhea, postprandial abdominal pain, and bloating, should be tested for CD.
  2. People with CD should adhere to a strict gluten-free diet for life.
  3. People with CD should be referred to a registered dietitian who is knowledgeable about CD in order to receive a thorough nutritional assessment and education on the GFD.
  4. People with newly diagnosed CD should undergo testing and treatment for micronutrient deficiencies. Deficiencies to be considered for testing should include, but not be limited to, iron, folic acid, vitamin D, and vitamin B12.
  5. Periodic medical follow-up should be performed by a health-care practitioner with knowledge of CD. Consultation with a dietitian should be offered if gluten contamination is suspected.
  6. People with CD should be monitored regularly for residual or new symptoms, adherence to GFD, and assessment for complications. In children, special attention to assure normal growth and development is recommended.
  7. Monitoring of adherence to GFD should be based on a combination of history and serology (IgA TTG or IgA (or IgG) DGP antibodies).
  8. Upper endoscopy with intestinal biopsies is recommended for monitoring in cases with lack of clinical response or relapse of symptoms despite a GFD.

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