Celiac disease is a
gluten-sensitive enteropathy, characterized by villous
atrophy, which is reversed by
gluten withdrawal. A minority of patients with celiac-like enteropathy are resistant to
gluten-free diet, so-called refractory
sprue, or unclassified
sprue. Refractory
sprue is a diagnosis of exclusion; all other causes of a celiac-like enteropathy must be eliminated before a diagnosis of refractory
sprue can be made. Recent evidence suggests that refractory
sprue comprises a heterogenous group of patients with diverse underlying causes. A small proportion of these patients seem to have an adult form of
autoimmune enteropathy, characterized by the presence of antienterocyte
antibodies. However, a larger group of patients with refractory
sprue now seem to have a cryptic intestinal
T-cell lymphoma, characterized by the presence of phenotypically abnormal, monoclonal intraepithelial lymphocytes, despite benign cytology. Current therapeutic options include
nutritional support and immunosuppressive therapy, but response is variable. The prognosis of refractory
sprue may be poor; patients may die of severe malabsorption, or through synchronous or metachronous development of an
enteropathy-associated T-cell lymphoma. Based on this recent evidence, patients with refractory
sprue should be screened for antienterocyte
antibodies and have
T-cell receptor and
monoclonal antibody studies performed; this could facilitate identification of cases of adult-onset
autoimmune enteropathy and those of cryptic
T-cell lymphoma. Moreover, early recognition of the malignant nature of the intestinal infiltrate in some cases of refractory
sprue could permit the development of novel chemotherapeutic regimens for this condition.