From the time of Gee's landmark writings, the recent history of
celiac disease (CD) can be divided into many ages, each driven by a diagnostic advance and a deeper knowledge of disease pathogenesis. At the same time, these advances were paralleled by the identification of new clinical patterns associated with CD and by a continuous redefinition of the prevalence of the disease in population. In the beginning, CD was considered a chronic
indigestion, even if the causative food was not known; later, the disease was proven to depend on an intolerance to wheat
gliadin, leading to typical mucosal changes in the gut and to a
malabsorption syndrome. This knowledge led to curing the disease with a
gluten-free diet. After the identification of
antibodies to
gluten (AGA) in the serum of patients and the identification of
gluten-specific lymphocytes in the mucosa, CD was described as an
immune disorder, resembling a chronic "
gluten infection". The use of serological testing for AGA allowed identification of the higher prevalence of this disorder, revealing atypical patterns of presentation. More recently, the characterization of
autoantibodies to endomysium and to
transglutaminase shifted the attention to a complex autoimmune pathogenesis and to the increased risk of developing autoimmune disorders in untreated CD. New diagnostic assays, based on molecular technologies, will introduce new changes, with the promise of better defining the spectrum of
gluten reactivity and the real burden of
gluten related-disorders in the population. Herein, we describe the different periods of CD experience, and further developments for the next celiac age will be proposed.