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Effects of Gluten-free Diet in Atypical Celiac Disease« Back to Volume 24, Issue 1, May 2008 - Table of Contents Celiac disease frequently presents growth impairments as evidenced by an inflammatory enteropathy from T-cell hypersensitivity to certain cereal antigens; catch-up growth may be induced by initiation of a gluten-free diet. Street et al sought to study children longitudinally over their first year on the diet. Children with atypical celiac disease (patients with typical gastrointestinal symptoms as well as in an atypical fashion) were followed; outcome measures included changes and correlations in growth parameters, insulin-like growth factor (IGF) axis members, and the proinflammatory cytokines implicated in celiac disease pathophysiology, interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Twenty children (9 male), aged 4.2 to 14.2 (mean 9.6) years at diagnosis of atypical celiac disease, were followed; 17 completed the one-year evaluations and 3 were lost to follow-up. Of note, all had atypical celiac disease and presented with recurrent abdominal pain, anemia, nausea, occasional vomiting, and fatigue, or were screened due to family history. None had diarrhea or malnutrition, 11 children were prepubertal at diagnosis, and during the year’s follow-up, 2 boys progressed from Tanner 2 to 3. Mean bone age at diagnosis was 9.4 years, SEM = 0.9 years. Eighteen healthy children (5 male), aged 5.6 to 14.6 (mean 11.1) years, matched for pubertal stage, were evaluated as controls at baseline (Table). Their bone age data were not available. The authors further examined various IGF/IGF binding protein (IGFBP) molar ratios, simple linear regression analyses and step-wise linear regression analyses to find additional correlates with baseline and treatment values. They concluded, “the data from this study confirm changes in the IGF and cytokine systems at diagnosis of celiac disease which tend to normalize on the gluten-free diet.” Editor’s CommentThere are several limitations to this study in considering the authors’ conclusions. The discussion section contains many conjectures about the mechanistic links between cytokines, IGF axis, growth, and disease of patients with celiac disease, stretching even to the increased risk of malignancy in patients with long-standing untreated celiac disease. All the data in this paper were associative. Associations are never sufficient to prove causation, as directionality and confounders remain unknown. There were no supporting mechanistic studies. Likewise, the paper measured serum concentrations. Local (ie, intestinal) concentrations of the cytokines and IGF axis members are more pertinent to disease activity, and changes may not be reflected in the serum levels. Finally, the study’s ability to generalize is limited. The subjects all had atypical celiac disease, so the results do not necessarily support conclusions about celiac disease in toto. However, it is this very limitation that makes the findings of this paper intriguing. None of the patients studied had diarrhea, signs of malnutrition or history of celiac crisis. Although the BMI at baseline was significantly lowered, it was still within the normal range. Likewise, the gluten-free diet improved the height z–score, which was already normal, and even better than target height, at baseline. The finding of significant alterations in serum cytokines, IGF-I and IGFBP-2 within this population speaks to the sensitivity of the IGF system to this disease process. Adda Grimberg, MD
« Back to Volume 24, Issue 1, May 2008 - Table of Contents
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Volume 24 Number 1
May 2008
www.GGHjournal.com
ISSN 1932-9032
