Dataset Information

Treatment Strategies for GLILD in Common Variable Immunodeficiency: A Systematic Review.

ABSTRACT:

Introduction

Besides recurrent infections, a proportion of patients with Common Variable Immunodeficiency Disorders (CVID) may suffer from immune dysregulation such as granulomatous-lymphocytic interstitial lung disease (GLILD). The optimal treatment of this complication is currently unknown. Experienced-based expert opinions have been produced, but a systematic review of published treatment studies is lacking.

Goals

To summarize and synthesize the published literature on the efficacy of treatments for GLILD in CVID.

Methods

We performed a systematic review using the PRISMA guidelines. Papers describing treatment and outcomes in CVID patients with radiographic and/or histologic evidence of GLILD were included. Treatment regimens and outcomes of treatment were summarized.

Results

6124 papers were identified and 42, reporting information about 233 patients in total, were included for review. These papers described case series or small, uncontrolled studies of monotherapy with glucocorticoids or other immunosuppressants, rituximab monotherapy or rituximab plus azathioprine, abatacept, or hematopoietic stem cell transplantation (HSCT). Treatment response rates varied widely. Cross-study comparisons were complicated because different treatment regimens, follow-up periods, and outcome measures were used. There was a trend towards more frequent GLILD relapses in patients treated with corticosteroid monotherapy when compared to rituximab-containing treatment regimens based on qualitative endpoints. HSCT is a promising alternative to pharmacological treatment of GLILD, because it has the potential to not only contain symptoms, but also to resolve the underlying pathology. However, mortality, especially among immunocompromised patients, is high.

Conclusions

We could not draw definitive conclusions regarding optimal pharmacological treatment for GLILD in CVID from the current literature since quantitative, well-controlled evidence was lacking. While HSCT might be considered a treatment option for GLILD in CVID, the risks related to the procedure are high. Our findings highlight the need for further research with uniform, objective and quantifiable endpoints. This should include international registries with standardized data collection including regular pulmonary function tests (with carbon monoxide-diffusion), uniform high-resolution chest CT radiographic scoring, and uniform treatment regimens, to facilitate comparison of treatment outcomes and ultimately randomized clinical trials.

SUBMITTER: Lamers OAC

PROVIDER: S-EPMC8086379 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundHypogammaglobulinemia may be part of several different immunological or malignant conditions, and its origin is not always obvious. Furthermore, although autoimmune cytopenias are known to be associated with common variable immunodeficiency (CVID) and even may precede signs of immunodeficiency, this is not always recognized. Despite novel insight into the molecular immunology of common variable immunodeficiency, several areas of uncertainty remain. In addition, the full spectrum of immunological effects of the B cell depleting anti-CD20 antibody Rituximab has not been fully explored. To our knowledge this is the first report of development of CVID in a patient with normal immunoglobulin prior to Rituximab treatment.Case presentationHere we describe the highly unusual clinical presentation of a 34-year old Caucasian male with treatment refractory immune thrombocytopenic purpura and persistent lymphadenopathy, who was splenectomized and received multiple courses of high-dose corticosteroid before treatment with Rituximab resulted in a sustained response. However, in the setting of severe pneumococcal meningitis, hypogammaglobulinemia was diagnosed. An extensive immunological investigation was performed in order to characterize his immune status, and to distinguish between a primary immunodeficiency and a side effect of Rituximab treatment. We provide an extensive presentation and discussion of the literature on the basic immunology of CVID, the mechanism of action of Rituximab, and the immunopathogenesis of hypogammaglobulinemia observed in this patient.ConclusionsWe suggest that CVID should be ruled out in any patient with immune cytopenias in order to avoid diagnostic delay. Likewise, we stress the importance of monitoring immunoglobulin levels before, during, and after Rituximab therapy to identify patients with hypogammaglobulinemia to ensure initiation of immunoglobulin replacement therapy in order to avoid life-threatening invasive bacterial infections. Recent reports indicate that Rituximab is not contra-indicated for the treatment of CVID-associated thrombocytopenia, however concomitant immunoglobulin substitution therapy is of fundamental importance to minimize the risk of infections. Therefore, lessons can be learned from this case report by clinicians caring for patients with immunodeficiencies, haematological diseases or other autoimmune disorders, particularly, when Rituximab treatment may be considered.