Fig. 15.21 The morphologic alterations that may be present in celiac disease, including varying degrees of villous atrophy, increased numbers of intraepithelial lymphocytes (IELs), and epithelial proliferation with crypt elongation (left). A model for the pathogenesis of celiac disease (right). Note that both innate and adaptive immune mechanisms are involved in the tissue responses to gliadin. CD4 T cells (producing IFNγ) are shown in lamina propria and CD8 T cells, expressing NKG2D receptor, in between epithelial cells.
enterocytes that have been induced by various stressors to express surface MIC-A. This molecule is recognized by the NKG2D receptor on activated CD8+ T cells. The damage caused by these immune mechanisms may increase the movement of gliadin peptides across the epithelium, which are then deamidated by tissue transglutaminase, thus perpetuating the cycle of disease.
While nearly all individuals eat grain and are exposed to gluten and gliadin, most do not develop celiac disease. Thus, host factors determine whether disease develops. Among these, HLA proteins seem to be critical, since almost all individuals with celiac disease carry the class II HLA-DQ2 or HLA-DQ8 alleles. There is also an association of celiac disease with other immune diseases including type 1 diabetes, thyroiditis, and Sjögren syndrome.
MORPHOLOGYBiopsyspecimensfromthesecondportionoftheduodenumorproximaljejunum,whichareexposedtothehighestconcentrationsofdietarygluten,aregenerallydiagnosticinceliacdisease.ThehistopathologyischaracterizedbyincreasednumbersofTlymphocytes,withintraepithelial lymphocytosis, crypt hyperplasia,andvillous atrophy (
Fig.15.22 ).Thislossofmucosalandbrush-bordersurfaceareaduetovillousatrophyprobablyaccountsforthemalabsorption.Inaddition,increasedratesofepithelialturnover,reflectedinincreasedcryptmitoticactivity,maylimittheabilityofabsorptiveenterocytestofullydifferentiateandexpressproteinsnecessaryforterminaldigestionandtransepithelialtransport.Otherhistologicfeaturesofceliacdiseasecanincludeincreasednumbersofplasmacells,mastcells,andeosinophils,especiallywithintheupperpartofthelaminapropria.Itshouldbenotedthatintraepitheliallymphocytosisandvillousatrophycanbepresentinotherdisorders,includingviralenteritis.Thecombinationofhistologicandserologicfindingsis,therefore,mostspecificfordiagnosisofceliacdisease.
Pediatric celiac disease, which affects male and female children equally, may manifest with classic symptoms, typically between 6 and 24 months of age (after introduction of gluten to the diet) with irritability, abdominal distention, anorexia, diarrhea, failure to thrive, weight loss, or muscle wasting. Children with nonclassic symptoms tend to present at older ages with complaints of abdominal pain, nausea, vomiting, bloating, or constipation. A characteristic pruritic, blistering skin lesion, dermatitis herpetiformis, is also present in as many as 10% of patients, and the incidence of lymphocytic gastritis and lymphocytic colitis is increased as well.