Classification and management of refractory coeliac disease

Abstract

Refractory celiac disease (RCD) is defined by persistent or recurrent malabsorptive symptoms and villous atrophy despite strict adherence to a gluten-free diet (GFD) for at least 6–12 months in the absence of other causes of non-responsive treated celiac disease (CD) and overt malignancy. Symptoms are often severe and require additional therapeutic intervention besides GFD. RCD can be classified as type 1 (normal intraepithelial lymphocyte phenotype), or type 2 (defined by the presence of abnormal [clonal] intraepithelial lymphocyte phenotype). Some patients with RCD may never have responded to a GFD or may have relapsed despite adherence and initial response to the GFD. RCD type 1 usually improves after treatment with a combination of aggressive nutritional support, adherence to GFD, and alternative pharmacologic therapies. By contrast, clinical response to alternative therapies in RCD type 2 is less certain and the prognosis is poor. Severe complications such as ulcerative jejunitis and enteropathy-associated T-cell lymphoma (EATL) may occur in a subgroup of patients with RCD. The aims of this article are (1) to review recent advances in the diagnosis and management of patients with RCD and (2) to describe current and novel methods for classification of patients with RCD into categories that are useful to predict outcome and direct treatment.

Diagnostic challenges in celiac disease

“…30 However, as much as 4-30% of patients have persistent symptoms, signs, or laboratory abnormalities in spite of 6-12 months of treatment. 2,3 These patients may be affected by non-responsive celiac disease (NRCD) and should be further diagnosed to find its cause.…”

“…31 Although positive CD serology often indicates gluten exposure, 19-30% of patients present positive serology despite complete gluten exclusion. 30 Moreover, negative serology may not reveal intermittent or low-level gluten intake. 3 Therefore, a detailed examination of the patient's diet by an expert dietitian in search for potential gluten sources is necessary.…”

“…Gluten ingestion is the most common cause of NRCD and is responsible for 36-51% of cases. 30 There is no objective laboratory method to detect gluten contamination. 31 Although positive CD serology often indicates gluten exposure, 19-30% of patients present positive serology despite complete gluten exclusion.…”

“…3,31 Endoscopic and imaging procedures should be employed to exclude malignancy as a cause of recurrent symptoms, particularly in patients presenting significant unexplained weight loss, bowel obstruction, gastrointestinal bleeding, anorexia, pruritus, fever, nocturnal diaphoresis or abdominal pain. 30 Finally, RCD remains diagnosis of exclusion (Fig. 2).…”

Is Refractory Celiac Disease More Severe in Old Europe?

“…A dietary inquiry performed by a dietician skilled in assessing GFD is mandatory for these particular patients, as no objective diagnostic tools (such as aberrant clonal IEL population for RCDII diagnosis) are available to distinguish RCDI from non-compliant classical celiac disease. Finally, other causes of villous atrophy may be fi rst eliminated, such as common variable immunodefi ciency or autoimmune enteropathy ( 21 ). Th e fi rst diff erential diagnosis may be not easy to exclude because of frequent prevalence of celiac disease-associated human leukocyte antigen (HLA)-DQ2 and / or -DQ8 genotypes found in up to 77 % of tested common variable immunodefi ciency patients with gastrointestinal symptoms ( 3 ).…”