Pediatric Celiac Disease (Sprue) Clinical Presentation

Updated: Jul 07, 2023
  • Author: Stefano Guandalini, MD, AGAF; Chief Editor: Carmen Cuffari, MD  more...
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Clinical presentation

Celiac disease (CD) may occur without any symptoms; asymptomatic or minimally symptomatic celiac disease is probably the most common form of the disease, especially in older children and adults.

Currently, five possible presentations of celiac disease are recognized, as follows [1, 2] :

  • Gastrointestinal (GI) manifestations: This presentation is primarily characterized by GI signs and symptoms.

  • Systemic and extraintestinal manifestations: GI signs and symptoms are minimal or absent, and various extraintestinal manifestations are present.

  • Silent: The small intestinal mucosa is damaged, and celiac disease autoimmunity can be detected with serology; however, no symptoms are present.

  • Potential: Patients have a positive specific autoimmune serology and may or may not be symptomatic, but the mucosa morphology is normal. These individuals have genetic compatibility with celiac disease, and full-blown celiac disease may develop at a later stage in some or all of these individuals.

  • Seronegative: Seronegative celiac disease (SNCD) refers to patients “with or without gastrointestinal signs and symptoms of CD in the presence of villous atrophy and compatible genetics and without IgA tTG, IgA DGP, and IgA EMA, who show clinical and histologic responses to the GFD and for whom other etiologies have been examined.” [36]  The prevalence of this condition (that at least in adults appears to have a more aggressive disease phenotype than seropositive celiac disease) is about 5% in adults but is much rarer in children.

GI manifestations

GI symptoms characteristically appear at age 9-24 months. Symptoms begin at various times after the introduction of foods that contain gluten. Infants and young children typically present with chronic diarrhea, anorexia, abdominal distension, abdominal pain, poor weight gain or weight loss, and vomiting. Severe malnutrition can occur if the diagnosis is delayed. Behavioral changes are common and include irritability and an introverted attitude. Rarely, severely affected infants present with a celiac crisis, which is characterized by explosive watery diarrhea, marked abdominal distension, dehydration, hypotension, and lethargy, often with profound electrolyte abnormalities, including severe hypokalemia.

Older children with celiac disease who present with GI manifestations may have onset of symptoms at any age. The variability in the age of symptom onset possibly depends on the amount of gluten in the diet and other environmental factors, such as duration of breastfeeding. In fact, in the author's experience, if gluten is introduced during breastfeeding, the symptoms tend to be less often GI related and tend to appear later in life. GI symptoms in older children are typically less evident and include nausea, recurrent abdominal pain, bloating, constipation, and intermittent diarrhea.

A study by Mårild et al reported a two-way association between anorexia nervosa and celiac disease. The hazard ratio for future anorexia nervosa after celiac disease diagnosis was 1.46 and 1.31 beyond the first year. The odds ratio for a previous anorexia nervosa diagnosis associated with celiac disease was 2.18. [37, 38]

Dental enamel hypoplasia: These enamel defects involve mostly the permanent dentition, although they have been described also in deciduous teeth. These changes may be the only presenting manifestation of celiac disease.

Aphthous ulcers: These can be present in children and in adults with celiac disease. At this time, it is unclear if these are associated with enamel defects, and their prevalence in celiac disease patients is variable. [39]  Oral ulcers are neither characteristic nor specific for celiac disease, since aphthous ulcers can also be associated with other medical conditions such as inflammatory bowel disease and Behçet disease. However, it should be noted that these ulcers often regress once the patients are on a gluten-free diet. [39]

Systemic and extraintestinal manifestations

An increasing number of patients are being diagnosed without typical GI manifestations at older ages. A reasonable assumption is that approximately 70% of patients with newly diagnosed celiac disease do not present with the typical major GI symptoms. Once again, a relationship between the age of onset and the type of presentation is noted; in infants and toddlers, GI symptoms and failure to thrive predominate, whereas during childhood, minor GI symptoms, inadequate rate of weight and height gain, and delayed puberty tend to be more common. In teenagers and young adults, anemia is the most common form of presentation. In adults and in the elderly, GI symptoms are more prevalent, although they are often minor. 

Table. (Open Table in a new window)

GI Manifestations

Systemic and Extra-GI manifestations

Abdominal distention

Abdominal pain






“Celiac crisis”

Aphthous ulcers/ Geographical tongue

Dental enamel hypoplasia


Weight loss/Failure to thrive


Vitamin D deficiency

Delayed puberty

Short stature

Dermatitis herpetiformis

Reduced bone mineral density

Arthritis, arthralgia

Abnormal liver enzymes/Autoimmune Hepatitis


  • Headaches, migraine
  • Peripheral neuropathy
  • Idiopathic seizures
  • Epilepsy (with or without occipital calcifications)


  • Irritability
  • Anxiety/Depression
  • ADHD symptoms

The main extraintestinal manifestations of celiac disease are as follows:

  • Iron-deficiency anemia: In several studies, iron-deficiency anemia that is resistant to oral iron supplementation is reportedly the most common extraintestinal manifestation of celiac disease in adults. In children, iron deficiency with or without anemia is very common too, but seldom is it seen as the only presenting sign. Anemia can only be the result of folate, vitamin B12 deficiency, and it may also coexist with anemia of chronic disease as a result of the chronic intestinal inflammation. In addition to anemia, a number of less common hematologic manifestations can be seen, including hyposplenism, thrombocytosis, and selective IgA deficiency. [40]

  • Short stature and delayed puberty: Short stature may be the only manifestation of celiac disease. As many as 10% of children with idiopathic short stature may have celiac disease that can be detected on serologic testing. Some patients with short stature also have impaired growth hormone production following provocative stimulation testing; this production returns to normal when the patient is put on a gluten-free diet. Adolescent girls with untreated celiac disease may have delayed onset of menarche.

  • Dermatitis herpetiformis: A blistering skin rash that involves the elbows, knees, and buttocks are associated with dermal granular immunoglobulin (Ig) A deposits. The rash and mucosal morphology improve on a gluten-free diet. Dermatitis herpetiformis is a rare occurrence in childhood and is described almost exclusively in teenagers and adults.

  • Hypertransaminasemia and autoimmune hepatitis: Patients with untreated celiac disease commonly have elevated transaminase levels (alanine aminotransferase [ALT], aspartate aminotransferase [AST]). [41] As many as 9% of patients with elevated transaminase levels of unclear etiology may have silent celiac disease. Liver biopsy findings in these patients reveal nonspecific reactive hepatitis. In most cases, liver enzymes normalize on a gluten-free diet. Autoimmune hepatitis occurs in less than 1% of individuals (mostly adults) [42]  but shows a much higher prevalence in celiac disease, where it affects between 2% and 6% of pediatric patients. [43]  The reverse is also true: in fact, about 15% of children with autoimmune hepatitis have been reported to have celiac disease. [44]  The response to the gluten-free diet has been reported sporadically and with conflicting outcomes.

  • Arthritis and arthralgia: Arthritis can be a common extraintestinal manifestation of adults with celiac disease, including those on a gluten-free diet. As many as 3% of children with juvenile chronic arthritis may have celiac disease.

  • Osteopenia and osteoporosis: Approximately 50% of children and 75% of adults have a low bone mineral density at the time of diagnosis; this low density reaches severe degrees, including osteoporosis. Bone mineral density improves in most patients on a gluten-free diet and returns to normal as soon as 1 year after starting the diet in children. However, the response to the diet can be much less marked in adults.

  • Neurological problems: Numerous neurological conditions have been attributed to celiac disease in adults and, to a lesser extent, in children. [45]  The most common neurological issue is headache/migraine. Celiac disease may cause occipital calcifications and intractable epilepsy; these patients can be resistant to antiseizure medicines but can benefit from a gluten-free diet if it is started soon after onset of seizures. The association with cerebellar ataxia is well described in adults; the term gluten-induced ataxia has been proposed.

  • Psychiatric disorders: Although a large number of behavioral problems and disorders (eg, autism, attention deficit hyperactivity disorder) have been thought to be caused by celiac disease, no evidence has been conclusive. However, celiac disease can be associated with some psychiatric disorders, such as depression and anxiety. [46]  These conditions can be severe and usually respond to a gluten-free diet.

  • Subfertility or infertility: Although somewhat controversial, reports have indicated that as many as 6% of women who experience infertility or repeated miscarriages have celiac disease. [47] Some studies recommend increased screening for celiac disease in pregnant women; however, screening is associated with its own risks and expense. Because of the potential serious effects of undiagnosed celiac disease on the outcome of pregnancy, the need for screening pregnant women for celiac disease is currently under investigation.

Associated diseases

Table. (Open Table in a new window)

Autoimmune conditions

Genetic/Chromosomal disorders

Other disorders

Type 1 diabetes mellitus

Thyroid disease:

  • Hashimoto thyroiditis
  • Graves-Basedow disease

Systemic lupus erythematosus

Juvenile idiopathic arthritis

Autoimmune skin disorders

  • Psoriasis
  • Vitiligo
  • Alopecia areata

Selective IgA deficiency

Down syndrome

Turner syndrome

Williams-Beuren syndrome

Eosinophilic esophagitis


Gastroesophageal reflux



The association of celiac disease with autoimmune conditions is well known. A strong positive correlation between the age at diagnosis and the prevalence of autoimmune disorders (eg, type 1 diabetes mellitus, thyroiditis, alopecia) is recognized; this suggests that the continuous ingestion of gluten before diagnosis may induce the development of other autoimmune conditions.

Type 1 diabetes mellitus

Approximately 10% of patients with type 1 diabetes mellitus have typical findings of celiac disease on duodenal biopsy samples.

Many individuals with type 1 diabetes mellitus who initially had negative serologic test results for celiac disease eventually had positive findings; this highlights the need for repeated testing.

Because celiac disease only occurs with specific human leukocyte antigen (HLA) haplotypes, an algorithm based on the determination of these HLA haplotypes has been proposed to avoid repeat testing in all patients with diabetes; this allows patients with diabetes in whom the HLA haplotypes are inconsistent with celiac disease to avoid repeat testing.

Typically, diagnosis of diabetes precedes diagnosis celiac disease by years; celiac disease in these patients most commonly presents with mild GI symptoms or absent symptoms. Because some of these symptoms are also seen in patients with diabetes (eg, bloating, diarrhea), diagnosis of celiac disease may be missed unless a screening is performed.

Although no convincing evidence has suggested that a gluten-free diet has any obvious effect on diabetes, these patients must follow the diet to prevent all long-term complications of celiac disease. Thus, screening patients with type 1 diabetes mellitus for celiac disease seems well founded.

Celiac disease is also known to be strongly associated with some genetic syndromes (eg, Down syndromeWilliams syndromeTurner syndrome).

Down syndrome

The best documented and most well-known nonautoimmune disorder associated with celiac disease is Down syndrome.

As assessed by screening methods, the prevalence of Down syndrome in celiac disease is 8-12%.Most patients with Down syndrome who have celiac disease have some GI symptoms, such as abdominal bloating, intermittent diarrhea, anorexia, or failure to thrive; however, about one third of these patients do not have GI symptoms.

As with patients who have type 1 diabetes mellitus, periodic serologic testing is indicated only in patients with Down syndrome who are genetically compatible with celiac disease (ie, those who have either HLA DQ2 or DQ8).

A similar strategy should be applied for patients with Turner syndrome or Williams syndrome, in whom an increased incidence of celiac disease has also been reported.

A study by Mårild et al found that in a review of pathology records of 7548 females with CD in Sweden, that 20 of the patients (0.26%) also had a diagnosis of Turner syndrome. In contrast, among 34,492 age- and sex-matched controls in the general Swedish population, only 21 (0.06%) had a Turner syndrome diagnosis, which corresponded to an odds ratio for celiac disease of 3.29 (95% confidence interval [CI], 1.94 - 5.56). [48, 49]

Juvenile idiopathic arthritis

A study by Doyle et al found in an analysis of nationwide Swedish data that pediatric patients with celiac disease were 2.7 times as likely to develop juvenile idiopathic arthritis (JIA), compared with children and adolescents in the general population. For those aged younger than 18 years, the incidence rate of JIA was 5.9 per 10,000 person-years among the 9415 patients with celiac disease versus 2.2 per 10,000 person-years in the general population, over a 7-year follow-up period. [50, 51]


Physical Examination

Examination findings depend on the extent of celiac disease, as follows:

  • Dry mucosal membranes with vomiting or diarrhea indicate the degree of dehydration.

  • Oral aphthae are more frequent than in normal population.

  • Dental enamel hypoplasia is a highly specific but relatively uncommon finding.

  • Bloating of the abdomen is a relatively common finding (see the image below).

    Potbelly and muscle wasting in a child with celiac Potbelly and muscle wasting in a child with celiac disease.
  • Muscle wasting is an obvious but uncommon finding and is part of the malnutrition that ensues because of the malabsorptive condition.

  • Celiac disease may occur in asymptomatic individuals without any positive clinical findings, as noted above.