Lessons Learned From the Clinical Presentation of Common Variable Immunodeficiency Disorders: A Systematic Review and Meta-Analysis.

Lisanne M A Janssen,Esther De Vries,Michiel Van Der Flier

doi:10.3389/fimmu.2021.620709

Abstract

BackgroundDiagnostic delay in common variable immunodeficiency disorders (CVID) is considerable. There is no generally accepted symptom-recognition framework for its early detection.ObjectiveTo systematically review all existing data on the clinical presentation of CVID.MethodsPubMed, EMBASE and Cochrane were searched for cohort studies, published January/1999-December/2019, detailing the clinical manifestations before, at and after the CVID-diagnosis.ResultsIn 51 studies (n=8521 patients) 134 presenting and 270 total clinical manifestations were identified. Recurrent upper and/or lower respiratory infections were present at diagnosis in 75%. Many patients had suffered severe bacterial infections (osteomyelitis 4%, meningitis 6%, septicemia 8%, mastoiditis 8%). Bronchiectasis (28%), lymphadenopathy (27%), splenomegaly (13%), inflammatory bowel disease (11%), autoimmune cytopenia (10%) and idiopathic thrombocytopenia (6%) were also frequently reported. A bimodal sex distribution was found, with male predominance in children (62%) and female predominance in adults (58%). 25% of CVID-patients developed other manifestations besides infections in childhood, this percentage was much higher in adults (62%). Immune-dysregulation features, such as granulomatous-lymphocytic interstitial lung disease and inflammatory bowel disease, were more prominent in adults.ConclusionsThe shift from male predominance in childhood to female predominance in adults suggests differences in genetic and environmental etiology in CVID and has consequences for pathophysiologic studies. We confirm the high frequency of respiratory infections at presentation, but also show a high incidence of severe bacterial infections such as sepsis and meningitis, and immune dysregulation features including lymphoproliferative, gastrointestinal and autoimmune manifestations. Early detection of CVID may be improved by screening for antibody deficiency in patients with these manifestations.

Highlights

Common variable immunodeficiency disorders (CVID) is a collection of heterogeneous clinical manifestations linked by low serum levels of immunoglobulins and primary failure of specific antibody production [1,2,3]
In order to improve our understanding of the early presentation of CVID, which can assist clinicians in timely detection of this condition, we focused our analysis on clinical manifestations at or prior to diagnosis
Recent studies already demonstrated a high incidence of antibody deficiency in patients with pneumococcal meningitis [86,87,88], confirming our finding of a high frequency of infectious meningitis in CVID, but we show a high incidence of bloodstream infections, mastoiditis and to a somewhat lesser extent osteomyelitis in CVID patients

Summary

Introduction

Common variable immunodeficiency disorders (CVID) is a collection of heterogeneous clinical manifestations linked by low serum levels of immunoglobulins and primary failure of specific antibody production [1,2,3]. CVID has a low prevalence in primary care and general hospital settings, where non-immunologists have little knowledge of this disease. Respiratory infections and non-infectious complications of CVID such as lymphoproliferation, granulomatous disease and autoimmunity are much more prevalent without concomitant CVID. This makes it challenging to front-line clinicians to recognize CVID in these cases. Diagnostic delay in common variable immunodeficiency disorders (CVID) is considerable. There is no generally accepted symptom-recognition framework for its early detection

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Conclusion