Refractory celiac disease(RCD)is a rare yet life-threatening form of celiac disease(CeD)that severely impacts patients' quality of life and poses significant therapeutic challenges.Based on the clonality of intraepithelial lymphocytes(IELs),RCD is classified into two subtypes:typeⅠRCD(RCDⅠ),characterized by polyclonal IELs infiltration,and type Ⅱ RCD(RCDⅡ),defined by monoclonal T-cell proliferation.RCDⅡ demonstrates significantly worse prognosis than RCDⅠ due to its association with monoclonal T-cell proliferation and high incidence of enteropathy-associated T-cell lymphoma(EATL).For RCD patients,gluten-free diet alone is often insufficient to achieve satisfactory therapeutic outcomes.This article reviewed recent advances in the treatment of RCD,including the optimization of conventional therapies and the roles of emerging therapies such as elemental diet,cladribine,mesalazine,biological agents,and autologous stem cell transplantation,aiming to provide insights and directions for clinical management of RCD.

Refractory celiac disease(RCD)is a rare yet life-threatening form of celiac disease(CeD)that severely impacts patients' quality of life and poses significant therapeutic challenges.Based on the clonality of intraepithelial lymphocytes(IELs),RCD is classified into two subtypes:typeⅠRCD(RCDⅠ),characterized by polyclonal IELs infiltration,and type Ⅱ RCD(RCDⅡ),defined by monoclonal T-cell proliferation.RCDⅡ demonstrates significantly worse prognosis than RCDⅠ due to its association with monoclonal T-cell proliferation and high incidence of enteropathy-associated T-cell lymphoma(EATL).For RCD patients,gluten-free diet alone is often insufficient to achieve satisfactory therapeutic outcomes.This article reviewed recent advances in the treatment of RCD,including the optimization of conventional therapies and the roles of emerging therapies such as elemental diet,cladribine,mesalazine,biological agents,and autologous stem cell transplantation,aiming to provide insights and directions for clinical management of RCD.