Presentation of Celiac Disease

The mode of presentation of patients with celiac disease has changed dramatically over the recent decades, with diarrheal or classic presentations becoming less common. This trend is most markedly seen in children, whose main presentations include recurrent abdominal pain, growth issues, and screening groups at risk. Among adults, presentations include diarrhea, anemia, osteoporosis, and recognition at endoscopy performed for gastroesophageal reflux disease, as well as screening. The groups most commonly screened include family members of patients with celiac disease, Down syndrome, and autoimmune diseases.

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Among children, celiac disease has a varied presentation, and is affected especially by the age at presentation.
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In addition to the diverse spectrum of disease presentations and age-related variability of the manifestations of celiac disease in children, the shifting presentation of the disease over time is recognized.
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While the list of conditions associated with celiac disease is quite extensive, there are several groups that are more frequently targeted for celiac disease screening because of their strong association.

Key Points

Children

Celiac disease was originally considered a pediatric disorder characterized by malabsorption and steatorrhea. Subsequently it was recognized that celiac disease could affect adults at any age, and, contrary to opinion at that time, children did not grow out of the disease. Most adults with celiac disease diagnosed before 1980 presented with diarrhea. With the advent of serologic tests in the 1980s, the wide spectrum of clinical manifestations became apparent.

Among children celiac disease has a varied presentation, and is affected especially by the age at presentation. Very young children present more often with “classic” celiac disease, characterized by diarrhea, abdominal distension, and failure to thrive. These younger patients are more likely to present with diarrheal or malabsorptive manifestations of the disease, whereas older children and adolescents are more likely to present with atypical gastrointestinal complaints such as pain, vomiting, or constipation. In addition, extraintestinal symptoms such as arthritis, neurologic symptoms, and anemia are not infrequent, as are asymptomatic cases. The authors’ experience shows that currently the vast majority of children with celiac disease present in 1 of the 3 following ways : (1) growth issues that include failure to thrive in the youngest children or short stature among older children ; (2) recurrent abdominal pain the cause of which is unclear, possibly related to episodic or transient intussusceptions that are being increasingly recognized to occur in both adults and children with celiac disease ; (3) at-risk children screened for the disease because either they were relatives of patients with celiac disease or they had one or more autoimmune disorders or Down syndrome. Based on our observation, only 9% of children present with diarrhea. In fact, diarrhea and the malabsorption syndrome are mainly evident in the very young (<2 years old). The authors’ experience differs from a series of pediatric patients from Spain in which 62% of the children presented with diarrhea.

In addition to the diverse spectrum of disease presentations and age-related variability of the manifestations of celiac disease in children, the shifting presentation of the disease over time is recognized. An overall decrease in the prevalence of diarrheal presentations over the past 2 decades, accompanied by an increase in atypical manifestations of the disease, has been well described in both adults and children. As an example of how much the presentation of celiac disease has changed, a recent study from the Netherlands revealed that celiac disease was more frequently represented in a cohort of children with chronic constipation fulfilling Rome III criteria for irritable bowel syndrome (IBS); celiac disease was more common than hypothyroidism and hypercalcemia as a cause of the constipation.

Overweight and obese children and adolescents with celiac disease are now frequently identified. The majority of North American children in the authors’ series had a normal body mass index; however, there were children who were overweight, only a minority of children studied were underweight. Similarly, adults may be obese at presentation of celiac disease.

More widespread use of serologic markers has facilitated the diagnosis of celiac disease in children. This fact alone does not entirely explain the decrease in diarrheal manifestations, as many long-term studies of adult and pediatric patients predating the use of these markers have documented this shift in clinical presentation. Of note, since the advent of sensitive and specific serologic assays over the past 2 decades, the gap between initial presentation of symptoms and diagnosis in symptomatic children has been gradually reduced. This reduction in duration of symptoms has also been documented in adults.

Breastfeeding practices appear to influence the mode of presentation in children, because children exclusively breastfed seem to less likely present with failure to thrive and short stature. Breast feeding also contributes to delaying the age of presentation of the disease and possibly preventing the disease. In addition, there is an association between cesarean delivery and development of celiac disease.

Adults

The major mode of presentation of celiac disease in adults is diarrhea, although this presentation occurs in fewer than 50% of patients. Other presentations include anemia, mainly caused by iron deficiency, though anemia due to nutritional factors and chronic disease may also be present at diagnosis of celiac disease. Anemia is more frequently seen at presentation in adults than in children.

Osteoporosis is another presentation of celiac disease in adults. Reduced bone density is common in patients with celiac disease, and there is increased risk of fracture. Research from Argentina demonstrated a high prevalence of bone fractures in the peripheral skeleton, mostly occurring before diagnosis or in noncompliant patients. Of interest, a population-based study from Sweden showed both adults and children with celiac disease were at increased risk of fracture. A study from the United States demonstrated an increased prevalence of celiac disease among osteoporotic patients. However, this finding was not confirmed by other studies from France and among postmenopausal women in Turkey.

Another mode of presentation is the incidental recognition of signs of villous atrophy caused by celiac disease during endoscopy performed for other indications. Most upper endoscopy procedures in adults are performed for gastroesophageal reflux disease (GERD). When celiac disease is recognized and treated in patients with GERD, improvement in the reflux is frequently noted. There is a reasonable argument for routine duodenal biopsies during endoscopy for adults, as is the usual practice for pediatric gastroenterologists.

Other presentations in adults include dermatitis herpetiformis, IBS, bloating, and chronic fatigue, as well as a variety of neurologic presentations. Many of the symptoms of celiac disease are common, frequently seen among patients attending primary care physicians. In the authors’ multicenter North American primary care screening study involving patients with a variety of symptoms including bloating, fatigue, recurrent abdominal pain, and IBS, screening for celiac disease resulted in a 40-fold increase in the rate of diagnosis of celiac disease.

Adults

Asymptomatic presentations

Serologic screening of groups at risk is undoubtedly responsible for the increased detection of celiac disease in children, some of whom are asymptomatic. Screening was the mode of diagnosis of about 25% of children seen in the authors’ center ; this includes those identified as a result of serologic screening of family members and those with associated autoimmune conditions. Similarly, for adults there has been an increased number of diagnoses attributable to screening of at-risk groups. At present, about 10% of those adults diagnosed with celiac disease seen in the Celiac Disease Center at Columbia University in New York presented through screening of at-risk groups. Not all of those individuals detected by screening are truly asymptomatic.

Several high-risk groups are commonly screened. The most frequently at-risk group screened is the group of family members of individuals with celiac disease. Several studies have shown that about 4% to 10% of first-degree relatives have the disease. The greatest risk is among siblings of affected individuals, but the risk extends to second-degree relatives as well. Other frequently screened groups include those with type 1 diabetes (3%–7%) and autoimmune liver disease.

The reason why some patients present with diarrhea whereas others are asymptomatic is not clear, for there is no correlation of a diarrheal presentation with severity of villous atrophy, nor length of bowel involved as assessed by video capsule endoscopy. Neurohumoral mechanisms may be important in determining the presence of symptoms, as patients with celiac disease had increased mucosal 5-hydroxytryptamine content and enhanced release from the upper small bowel, which correlated with postprandial dyspepsia.

Associated conditions

Although the list of conditions associated with celiac disease is extensive, several groups are more frequently targeted for celiac disease screening because of their strong association. The association between celiac disease and type 1 diabetes in children is well described. The coexistence of both diseases also occurs in adults. The onset of diabetes generally precedes that of celiac disease. An increased prevalence of celiac disease has also been described in adults and children with autoimmune thyroid disease.

Children and adolescents with autoimmune liver disease, including biliary disease, have a high prevalence of celiac disease. An increased prevalence of celiac disease has additionally been identified in children with Down syndrome (7%), Turner syndrome (6.4%), and Williams syndrome (9.5%).

Several other conditions have been associated with celiac disease, including: autoimmune myocarditis; idiopathic dilated cardiomyopathy; Sjögren syndrome; immunoglobulin A (IgA) deficiency; Addison disease; IgA nephropathy; sarcoidosis; primary hyperparathyroidism; alopecia areata; vitiligo; neurologic abnormalities including epilepsy, ataxia, and neuropathy; atopy; inflammatory bowel disease; psoriasis; and chronic urticaria.

The association with celiac disease and autoimmune disorders is strong. About 30% of adult patients with celiac disease have one or more autoimmune disorder, compared with about 3% in the general population. The mechanism of these comorbidities is unclear. It has been suggested that the increase is associated with the duration of exposure to gluten, although this hypothesis has not been corroborated by other studies. In a study from France, however, after the diagnosis of celiac disease those who were strictly adherent to the gluten-free diet acquired fewer autoimmune disorders than those who were not compliant with the diet. This finding indicates that the diet may be protective against the development of autoimmune diseases. However, the institution of a gluten-free diet did not prevent progression of established autoimmune thyroid disease after the diagnosis of celiac disease.

Celiac disease is also associated with infertility in both women and men. Screening of infertile women detects undiagnosed celiac disease. Fertility improves after diagnosis of celiac disease.

Terminology and definitions

There have been several terms used to classify the presentations of celiac disease in both childhood and adulthood. Such terms as typical, atypical, classic, nonclassic, silent, asymptomatic, latent, and potential celiac disease have added confusion to the topic. Two extensive reviews have been published recently in an attempt to bring clarity and agreement to the field.

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