A small proportion of coeliac disease (CD) patients fail to improve after a
gluten-free diet (GFD) and may be considered as atypical regarding their outcome (refractory coeliac disease). The aim of this study is to diagnose and manage patients with CD who fail to improve after a GFD. Refractory coeliac disease (RCD) is a
malabsorption syndrome defined by persisting villous
atrophy with, usually, an increase of intraepithelial lymphocytes (IELs) in the small bowel in spite of a strict GFD and comprises a heterogenous group of diseases. Some of these diseases have to be excluded and can be treated by specific
therapies like
antibiotics in
tropical sprue and
giardiasis and
immune globulin substitution in
common variable immunodeficiency, while other
malabsorption syndromes are less well defined and may require immunosuppressive therapy. Standardized treatment, however, has not been evaluated in such patients so far. In a subgroup of patients with RCD, an abnormal intraepithelial lymphocyte (IEL) population may be observed with the lack of surface expression of usual T-cell markers (CD3-CD8 and/or the
T-cell receptor (TCR)) on IELs associated with T-cell clonality pattern suggest the presence of an early
enteropathy-associated T-cell lymphoma (EATL) in a subgroup of patients with RCD. This hypothesis has been supported by studies, which revealed progression into overt intestinal
T-cell lymphomas in a subgroup of RCD.
Steroid treatment has been reported effective even in patients with underlying early EATL. However, long-term results are unsatisfactory in most of these patients with RCD and
parenteral nutrition has to be applied in some of these cases. First results with more aggressive
chemotherapies and use of
cytokines are under way. Due to the difficulty of diagnostic and therapeutic regimens patients should be referred to tertiary centres for coeliac disease.