How should we define celiac disease?

Abstract

To the Editor: The patient described by Valetta et al. (1) clearly illustrates the frustration of patients and physicians in making a definitive diagnosis of celiac disease. Conventional clinical wisdom dictates confirmation of the diagnosis of celiac disease by definitive intestinal histology before beginning a gluten-free diet (2). Our studies on the genetics of celiac disease have clearly been compromised by individuals who have chosen gluten restriction on the basis of clinical symptoms to avoid the intestinal biopsy procedure (3). Such self-prescription of a gluten-free diet may subject individuals who do not actually have the disease to unnecessary dietary restriction and expense, and also to the uncertainty of whether a gluten-free diet is absolutely necessary. However, parents, patients, and physicians become frustrated when symptoms and complications of likely celiac disease persist. In families with known celiac disease, unprescribed gluten restriction will almost certainly result. Gluten restriction will influence subsequent biopsies, and a definitive biopsy diagnosis may never be made. We agree that biopsy should ideally be preceded by a liberal unrestricted diet or a gluten challenge, but in reality that may not be possible in light of a frustrated family and patient as described by Valetta et al. The celiac disease histologic lesion ranges from Marsh grade I with normal villus height and increased intraepithelial lymphocytes to Marsh grade III with subtotal or total villus atrophy (4,5). The entire spectrum of the gluten-sensitive small intestinal histologic lesions has been defined in patients with the extraintestinal manifestation of gluten-sensitive enteropathy, dermatititis herpetiformis (6,7). Many of the Marsh grade I and II biopsy specimens seen in that disorder would not be called positive if they were seen without the skin disease. Yet both the skin disease and the small bowel lesion improve with gluten restriction (8). Should, however, someone with positive results of a serology test and Marsh I or II histologic abnormalities also be considered as having gluten-sensitive enteropathy, as are patients with dermatitis herpetiformis and similar intestinal lesions? In recommending reevaluation, how many individuals will be lost to follow-up or refuse subsequent biopsy? Perhaps it is time to reconsider the criteria for diagnosing celiac disease and to base diagnosis on multiple criteria. The presence of IgA endomysial or tissue transglutaminase antibodies is a very sensitive and specific serologic predictor of gluten-sensitive enteropathy (9,10). In the current case, it was clearly a better predictor of celiac disease than was intestinal biopsy. In retrospect, there is little question that this patient had complications of celiac disease during the entire course of the illness described by the authors. Other factors, which greatly increase the likelihood of celiac disease, include the presence of unexplained iron deficiency, a first-degree relative with celiac disease, presence of the HLA DQ2 genotype, intestinal permeability tests, antigliadin antibodies, and decreased growth. Kaukinen et al. (11) recently described 10 adults who satisfied many of these criteria but demonstrated only minor mucosal inflammation. Their patients showed clinical, histologic, and serologic recovery on a gluten-free diet. They felt that the risk of complications warranted dietary treatment and we agree. We do a disservice to our patients by letting them languish with symptoms and risk complications while we await a diagnostic small bowel biopsy. The responsibility to improve the diagnostic criteria and resolve this conundrum rests clearly on the shoulders of clinical investigators and should be pursued vigorously to alleviate unnecessary complications in our patients. Linda Book Susan Neuhausen John Zone