Journal of Pediatric Gastroenterology & Nutrition:
Department of Paediatric Gastroenterology and Nutrition, Hospital Infantil Universitario La Paz, Facultad de Medicina, Universidad Autónoma, Madrid, Spain
Address correspondence and reprint requests to Isabel Polanco, MD, PhD, Department of Paediatric Gastroenterology and Nutrition, Hospital Infantil Universitario La Paz, Universidad Autónoma, Madrid, Spain (e-mail: firstname.lastname@example.org).
The author reports no conflicts of interest.
Celiac disease is an immunologically mediated enteropathy of the small intestine, characterized by lifelong intolerance to the gliadin and related prolamines from wheat and other cereals, that occurs in genetically predisposed individuals. Symptoms result from structural damage to the mucosa of the small intestine, which may cause malabsorption with positive autoantibodies in the sera. Normal mucosal architecture is restored after the use of a gluten-free diet and the normalization of the autoantibodies. Villous atrophy and high levels of autoantibodies reappear when gluten is reintroduced into the diet (gluten challenge).
The true incidence of celiac disease (CD) in susceptible populations may be dramatically higher than has been previously recognized (1–4). Most cases remain undiagnosed unless actively identified through mass serological screening. CD affects female individuals more than male individuals (ratio 2:1). A relationship between a diagnosis of CD and various factors (genetic background, quality and quantity of gluten, age at introduction of gluten, and breast-feeding) has been described (5–7).
The primary association of CD is the HLA-DQ dimer DQA1*0501/DQB1*0201. The majority of patients and first-degree relatives (and ≤20% of normal control individuals in susceptible populations) may express this dimer on antigen-presenting cells. The possession of this haplotype is not enough to cause gluten-induced changes, and the administration of extra gluten to HLA-identical siblings of CD patients does not always result in pathological changes to the intestine. The HLA-DQ dimmer is also strongly linked to HLA-DR status (8).
The proximal mucosa of the small intestine in patients with CD becomes abnormal on gluten ingestion, and small bowel biopsy is essential to confirm the diagnosis. The abnormality is characterized by stunted villi or even absence of villi associated with an increase in crypt length and cell numbers—the so-called flat mucosa. The flat gut lesion is characteristic of CD but is nonspecific (Table 1). Figure 1 (9).
All structural damage resolves on gluten withdrawal but recurs if gluten is reintroduced to the diet. Similar intestinal changes are frequently found in dermatitis herpetiformis, an intensely itchy, chronic, papulovesicular skin disorder caused by granular subepithelial IgA deposits in the upper dermis. Both the cutaneous and the intestinal lesions regress with a gluten free-diet. Dermatitis herpetiformis is now considered to be a specific skin manifestation of CD.
Celiac disease can have different clinical manifestations.
In general, the first symptoms appear during the months after the introduction of gluten in the diet. The earlier gluten is introduced, the shorter the interval between introduction and occurrence of the first symptoms. The first symptoms of CD, therefore, traditionally occur between 12 months and 3 years of age (Table 2).
In a minority of children, diagnosis is not made by the age of 5 years. CD can therefore be diagnosed at any time up to adulthood, because symptoms have been either ignored or misinterpreted (eg, short stature), because the disease is truly symptomless, or when some other autoimmune disease occurs (Tables 3 and 4).
Latent Celiac Disease
Individuals with CD may present with a severe or mild enteropathy at different times of their life. In fact, some individuals have had normal jejunal biopsy results while taking a normal diet but at some other time have had a flat jejunal biopsy specimen and recovered while using a gluten-free diet. For such individuals, the definition of latent CD has been proposed. This definition can also be applied to “late relapsers” (10–12).
The diagnosis of CD requires both a jejunoduodenal biopsy specimen that shows the characteristic findings of intraepithelial lymphocytosis, crypt hyperplasia, and villous atrophy (Figure 1) and a positive response to a gluten-free diet. The diagnostic criteria developed by the European Society for Pediatric Gastroenterology and Nutrition (2) require only clinical improvement with the diet, although histological improvement with a gluten-free diet is frequently sought and is recommended for adults because villous atrophy may persist despite a clinical response to the diet. In most patients, the diagnosis is easily established. However, roughly 10% of cases are difficult to diagnose because of a lack of concordance among the serological, clinical, and histological findings (1–3).
The most sensitive antibody tests for the diagnosis of CD are of the IgA class. The recognition that the enzyme tissue transglutaminase is the autoantigen for the development of endomysial antibodies has allowed the development of automated enzyme-linked immunoassays that are less expensive than the endomysial antibody test. Overall, the sensitivity of the tests for both endomysial antibodies and anti–tissue transglutaminase antibodies is greater than 90%, and a test for either marker is considered the best means of screening for CD (Table 5). The titers of endomysial antibodies and anti–tissue transglutaminase antibodies correlate with the degree of mucosal damage; as a result, the sensitivity of these antibody tests declines when a greater number of patients with lesser degrees of villous atrophy are included in studies. The various commercially available assays for anti–tissue transglutaminase antibodies have different characteristics and resultant sensitivities and specificities.
A strict gluten-free diet with lifelong exclusion of gluten from wheat, rye, barley, and oats must be recommended for both symptomatic and asymptomatic individuals. Lifelong adherence to a strict gluten-free diet should be advised for all children with CD to avoid the late complications of the disease (13). Adherence to a strict gluten-free diet is essential but not easy, and follow-up monitoring by a gastroenterologist about once a year seems to be advisable. CD patients' associations help patients to adhere to a gluten-free diet and to understand their disease better.
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