This study showed that CD affects the proximal small intestine and extends distally for a variable distance in a more or less continuous fashion and also heals in the reverse direction after gluten withdrawal. The study confirmed that most patients have a continuous pattern of atrophy, almost always observable in the duodenum. Just 1 patient did not have observable atrophy changes on the duodenal images with atrophy being seen only in the jejunum. Although these data support the concept that CD affects predominantly the proximal small intestine,32
it also showed that CD can be quite variable in its distribution and in the extent of involvement in the intestine.
It has long been known that the mode of presentation and/or the severity of CD are not predicted by the severity of mucosal damage that is found on biopsy specimens of the proximal small intestine.1,3
Rather, it has been suggested that it is the variation of the extent of involvement of the intestine that may predict the clinical severity of malabsorption.4,33
This study suggested that this is not the case, the extent of visual changes did not correlate with the clinical severity of CD, body mass index, age, or sex. The only previous study that examined the extent of intestinal involvement (in vivo) and its influence on the symptoms of CD was performed using a multiple biopsy device and fluoroscopy in the early 1960s. This study was limited because it included only a small number of patients and because it included only patients with frank malabsorption.5
Necropsies on patients with predominantly complicated CD in the early 1970s confirmed that the mucosal lesion in adult CD involved the duodenum and jejunum and only occasionally extended into the ileum and that the flat lesion persists to a lesser extent in a proportion of cases after GFD.34
Our larger set of patients encompassed a broad range of clinical presentations that more completely represent the current spectrum of CD.
Other factors may be more important for the understanding of what predicts severity of CD. One explanation could be the gene dose effect of the HLA-DQ2 alleles. Indeed, the homozygosity for the DQB1*0201 allele was associated with a more severe form of CD assessed by more severe villous atrophy, slower recovery of villous atrophy after a GFD, younger age, more severe diarrhea, and a lower level of blood hemoglobin at the time of diagnosis.35
An additional factor may be the gastrointestinal motility disturbances associated with untreated CD, which can play a role in the genesis of gastrointestinal symptoms and disappear after gluten withdrawal.36
Studies in children have shown that improvement and, indeed, return to normality may occur relatively quickly within weeks to months of the institution of a GFD.37
However, a high proportion of adults may not heal their intestinal abnormalities even after a year or more of a GFD.25-27,38,39
Our results in an adult population suggest that mucosal improvement is readily apparent after gluten withdrawal by 6 months, with a reduction in the frequency and distribution of features of atrophy in both the duodenum and jejunum. Biopsy specimens of the proximal small intestine alone may not reflect the healing that has occurred more distally in response to a GFD. Capsule endoscopy, in our study, showed that healing in the small intestine occurred from a distal to proximal direction with most residual changes remaining in the duodenum. The reasons for this finding are unclear, but may reflect a greater exposure of the duodenum to gluten and the disease-inducing peptides that could produce greater or more long-lasting changes in the mucosa compared with more distal involvement.5
This was a single-center study susceptible to both referral and regional bias; however, the inclusion of consecutive cases may have decreased the risk of selection bias.
In summary, this study, using WCE, showed the predominantly proximal distribution of visible features of atrophy in untreated CD and a significant reduction in the extent of involvement in response to a GFD, with some residual changes limited to the duodenum. This study strongly suggested that the extent of the enteropathy alone does not explain the wide clinical spectrum that characterizes CD.