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Refractory celiac disease: from bench to bedside.

Georgia Malamut1, Bertrand Meresse, Christophe Cellier

  • 1INSERM, U989, Paris, France.

Seminars in Immunopathology
|July 20, 2012
PubMed
Summary

Refractory celiac disease (RCD) persists despite a gluten-free diet, with two types identified: Type I RCD and Type II RCD, a lymphoma with a poor prognosis. Understanding RCD mechanisms is key for improved treatment.

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Area of Science:

  • Gastroenterology
  • Immunology
  • Oncology

Background:

  • Refractory celiac disease (RCD) is characterized by persistent malnutrition and villous atrophy despite a strict gluten-free diet (GFD).
  • Diagnosis involves excluding other causes of chronic small intestinal inflammation and ensuring no inadvertent gluten intake.
  • Over 15 years, multidisciplinary approaches have distinguished two RCD entities.

Purpose of the Study:

  • To review the distinct characteristics of Refractory Celiac Disease Type I (RCD I) and Type II (RCD II).
  • To explore mechanisms underlying resistance to a gluten-free diet (GFD).
  • To discuss the risk of high-grade lymphoma transformation and potential treatment improvements.

Main Methods:

  • Literature review of multidisciplinary approaches and clinical characteristics of RCD.
  • Analysis of immunological and genetic features of intraepithelial lymphocytes (IEL) in RCD.
  • Comparative assessment of RCD I and RCD II prognosis and progression.

Main Results:

  • RCD II is a low-grade intraepithelial lymphoma with abnormal IEL, aberrant NK/T cell phenotype, clonal T cell rearrangements, and a severe prognosis due to lymphoma transformation.
  • RCD I involves intestinal lymphocytes with a normal phenotype, presenting a milder condition often difficult to distinguish from uncomplicated celiac disease (CD) solely by GFD resistance.
  • Mechanisms for GFD resistance vary, with RCD II carrying a significant risk of overt aggressive enteropathy-associated T cell lymphoma.

Conclusions:

  • RCD I and RCD II represent distinct entities with differing prognoses and underlying pathologies.
  • Identifying the mechanisms of GFD resistance is crucial for managing RCD.
  • Further research into RCD II is needed to improve the poor prognosis and reduce the risk of lymphoma transformation.