Diagnosis Of Celiac Disease

Background

Celiac disease is a chronic inflammatory disease predominantly affecting the small bowel resulting from an immune-mediated intolerance to ingested gluten, the storage proteins of wheat [1]. Clinical manifestations include diarrhea and numerous other sequelae of malabsorption, non-specific gastrointestinal disturbance, and a host of extraintestinal phenomena, affecting the skin, joints, teeth, nervous system, energy level, and mood. The clinical presentation has changed with fewer patients presenting with diarrhea [2]. Celiac disease was once considered rare in the United States. However, a study involving 2000 healthy blood donors found serologies suggestive of celiac disease in 1 in 250 subjects [3]. A recent large, multicenter study investigating the prevalence of celiac disease, the first of its scale in the United States, revealed biopsy-proven prevalence rates of 1 in 133 asymptomatic subjects without known family histories of the disease [4]. These rates are similar to those reported in Europe [5]. Most recently a prevalence rate of 1 in 99 Finnish school children has been published [6]. However, the prevalence of diagnosed celiac disease in the United States has been reported to be approximately 1 in 5000 [7]. Based on these discrepancies, it is apparent that celiac disease is underdiagnosed in the United States.

Importance of timely diagnosis

The average length of time between onset of symptoms and the diagnosis of celiac disease has decreased from 9 years for patients diagnosed prior to 1990 to 4.4 years for patients who were diagnosed after 1993 [2]. Although this change likely reflects the advent of serologic tests and growing awareness of celiac disease, the persistent lag between symptoms and diagnosis leaves much room for improvement. Several studies have demonstrated that the diagnostic delay was physician related rather than delay in patients seeking health care [8-10]. Timely diagnosis of celiac disease has implications beyond the relief of symptoms in affected patients. Silent manifestations of celiac disease, including osteoporosis, iron and folate deficiency will be screened for and detected once diagnosis of celiac disease is established. The increased mortality in patients with celiac disease, largely due to non-Hodgkin's lymphoma, can be reduced by prompt diagnosis and strict adherence to a gluten-free diet [11]. Because the duration of gluten exposure corresponds with the risk of developing concomitant autoimmune disease [12] early diagnosis is obviously favored.

Clinical features of celiac disease

Symptoms that should obviously arouse suspicion for celiac disease include diarrhea and irritable bowel syndrome. In fact, 5% of those with IBS had a diagnosis of celiac disease established after serologic screening for celiac disease [13]. The list of associated diseases is great (Table 1). The burden is on the physician to consider the diagnosis in any variety of conditions, perform the appropriate serologic screening and refer for biopsy. DIAGNOSIS OF CELIAC DISEASE DEPENDS ON AN ABNORMAL SMALL INTESTINAL BIOPSY TOGETHER WITH CLINICAL RESPONSE TO A GLUTEN-FREE DIET. These criteria were established by the European Society of Pediatric Gastroenterology and Nutrition [14] and have been extrapolated to adults. Of note the criteria require an initial biopsy and not a follow up biopsy, though this is commonly performed especially in adults to document healing when the classical, diarrhea predominant presentation is lacking. Serologic testing facilitates the diagnosis of celiac disease but is not part of the diagnostic criteria.

The clinical features have changed with fewer patients presenting with diarrhea. This is seen in Figure 1, in which the mode of presentation of patients who were diagnosed prior to 1990 is represented, 75 percent of this group presented with diarrhea. This compares with those diagnosed after 1990, in which less than 50 percent presented with diarrhea (Figure 2).

Figure 1

Figure 2

These groups were adults seen at Columbia University Medical Center. The change in mode of presentation was attributed to both increased awareness of the variety of clinical manifestations and the use of serologic tests.

Conclusion

Celiac disease is more common in the United States than previously thought, and there is evidence that it is underdiagnosed. Identification of patients with celiac disease requires awareness of the gastrointestinal and systemic manifestations of this disease. Although no single serologic test is ideal, using several tests used in concert can provide effective screening in patients with suspected celiac disease. When clinical suspicion is high, negative serologies does not exclude the diagnosis, and the clinician should proceed with a duodenal biopsy. Positive serologies also require biopsy confirmation of the presence of celiac disease. Prompt diagnosis and treatment with a lifelong gluten-free diet mitigates and even reverses the gastrointestinal and systemic effects of celiac disease, and reduces the risks of subsequent development of malignancy.