Recommendations for the evaluation of CNS disease in antibody deficiencies
December 17, 2019
Common variable immunodeficiency (CVID) is the most prevalent symptomatic human primary antibody deficiency world-wide. The genetic defect is unknown in the majority of CVID patients. Besides recurrent bacterial infections, CVID patients may develop non-infectious disease complications due to aberrant activation of their immune system. These complications include splenomegaly, autoimmune cytopenia, enteropathy and malignancies. In rare cases, the central nervous system (CNS) is involved. This is a potentially severe complication for which diagnostic and therapeutic protocols are lacking.
Van de Ven et al. reviewed the clinical manifestations, genetic and immunological characteristics, diagnostic evaluation and treatment of CVID patients with CNS disease in their cohort at the University of Freiburg, Germany. Their findings were recently published in The Journal of Allergy and Clinical Immunology: In Practice.
They identified seventeen patients with CNS disease and a previous diagnosis of CVID. 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.
Compared to control CVID patients, the patients with CNS disease more often suffered from splenomegaly, lymphadenopathy, interstitial lung disease and autoimmune cytopenia. They generally displayed more severe lymphocytic abnormalities than control CVID patients.
In 8 patients, a molecular defect was identified, including mutations in CTLA4, NFKB1 and CECR1. Regarding treatment, CNS involvement usually responded well to high-dose steroids. In order to prevent relapse however, maintenance immunosuppressive therapy was regularly required.
The authors concluded that CNS disease is a rare but often severe disease manifestation as part of a systemic immune dysregulation. They provide recommendations for diagnosis, follow-up and treatment of CNS disease in CVID patients. Since the susceptibility to infections is increased, ruling out an infectious cause of the disease is mandatory. A genetic evaluation is strongly recommended since the probability for an underlying monogenic disorder is high.
The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.