Patients presenting with silent CD, without gastrointestinal (GI) symptoms, may have short stature or neurologic symptoms and possible reproductive disorders, including delayed menarche, menstrual disturbances, infertility, and recurrent miscarriage.1,4,5 Patients with obvious or clinically relevant disease may also have these findings. Risk factors include family history, type 1 diabetes mellitus, autoimmune thyroid disease, Down syndrome, and Turner syndrome (Table 1).1,2 Celiac disease has also been associated with chronic pelvic pain, including dysmenorrhea and deep dyspareunia.6
Individuals with gluten intolerance may have CD, a wheat allergy, or gluten sensitivity. All involve a gastrointestinal or dermatologic reaction to the gluten protein found in wheat, rye, and barley. The clinical presentation may be identical, but wheat allergy typically has a more abrupt onset. Only CD is associated with enteropathy; wheat allergy and gluten sensitivity are not associated with coexisting conditions.
The underlying injury involves an inflammatory reaction, primarily in the duodenum and jejunum, mediated by gliadin reactive CD4+ T cells in the lamina propria. These cells bind to gliadin, a primary wheat protein, and produce inflammatory cytokines, especially interferon-γ.7 The immunogenicity of gliadin is enhanced by the enzyme tissue transglutaminase, which dimidiates the gliadin peptides and serves as a marker for CD. The ensuing cascade of events involves release of several toxic mediators, including metalloproteinases, which ultimately produce hyperplasia of the crypts and injury of the villi. As the damage progresses, the enterocytes are lethally injured, and absorption is impaired.
The mechanisms by which CD affects reproduction are unknown, and indeed, not all studies examining the relationship have consistently found adverse effects. Nutritional and other factors have been suggested but do not appear to be involved in patients with silent CD.