Structural non-infectious manifestations of the central nervous system in common variable immunodeficiency disorders

Structural non-infectious manifestations of the central nervous system in common variable immunodeficiency disorders:

Publication date: Available online 16 December 2019

Source: The Journal of Allergy and Clinical Immunology: In Practice

Author(s): Annick van de Ven, Irina Mader, Daniel Wolff, Sigune Goldacker, Hannah Fuhrer, Sebastian Rauer, Bodo Grimbacher, Klaus Warnatz

Abstract

Background

Central nervous system (CNS) disease in adult common variable immunodeficiency (CVID) is rare and therefore diagnostic and therapeutic protocols are lacking.

Objective

To provide clinical information aiming to establish awareness and first experience-based recommendations.

Methods

We reviewed clinical manifestations, genetic and immunological characteristics, diagnostic evaluation and treatment of CVID patients with abnormal magnetic resonance imaging (MRI) of the CNS disease in our cohort.

Results

Seventeen patients with CNS manifestation and a previous diagnosis of CVID were identified. Presenting symptoms of the CNS disease included loss of sensory or motoric function, headache or epilepsy. Contrast-enhancing lesions of the brain or solely the spinal cord were the most common findings on MRI.

The prevalence of splenomegaly, lymphadenopathy, interstitial lung disease and autoimmune cytopenia was significantly increased compared to control CVID patients. In eight patients, a molecular defect was identified, including mutations in CTLA4, NFKB1 and CECR1. CVID patients with CNS involvement generally displayed lymphopenia, skewed CD4⁺ T-cell subsets and increased proportions of CD21^low B cells in the peripheral blood. CNS involvement usually responded well to high-dose steroids, but regularly required maintenance therapy in order to prevent relapse.

Conclusion

CNS disease is a severe but rare complication in CVID disorders, particularly affecting patients with other non-infectious disease symptoms. Diagnostic evaluation needs to rule out infectious causes by all means; a genetic evaluation is recommended given the high probability of an underlying monogenic disorder. Possible treatment consists of steroids with yet to be determined optimal maintenance therapy in case of relapse.