Clinical and immunological features of 44 common variable immunodeficiency patients: the experience of a single center in Turkey

Abstract

Introduction and objectives

Common variable immunodeficiency (CVID) is one of the most prevalent forms of primary immunodeficiency characterized by hypogammaglobinemia. Its heterogeneous clinical features include recurrent respiratory tract infections and other complications such as gastrointestinal, autoimmunity, and lymphoproliferative disorders. The aim of this article is to evaluate the general characteristics of CVID patients.

Materials and methods

Clinical and immunological features of 44 CVID patients were evaluated retrospectively with long-term follow-up. Patients who participated in the study were diagnosed according to the criteria of the European Society for Immunodeficiency Diseases (ESID).

Results

The median age at onset of symptoms was 2.75 years (range 6 months to 17 years), and the median age at diagnosis was 7.75 years (range 4–20 years). The average delay in diagnosis was 4.6 years (range 1–14 years). Positive family history was 18.2%. Before treatment, patients’ median total serum IgG was 271.5 mg/dL, median IgA was 7.5 mg/dL, and median IgM was 21 mg/dL. Infections were the most common clinical manifestation, and 63.6% of patients presented with sinopulmonary infection as the first manifestation. Bronchiectasis developed in 23 CVID subjects, while bronchiectasis was detected prior to CVID diagnosis in eight patients. All patients received immunoglobulin replacement therapy, and one patient died because of granulomatous lymphocytic interstitial lung disease (GLILD).

Conclusions

CVID is a heterogeneous group of immunologic disorders with unknown etiology. There are significant differences in the clinical presentation and prevalence of CVID-related complications among countries. Local guidelines for diagnosis and clinical follow-up are needed.

Introduction

Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency disease, characterized by hypogammaglobinemia, recurrent bacterial infections, and chronic complications.¹ There are no exact data available, but the estimated prevalence of CVID is between 1:25,000 and 1:50,000, affecting men and women equally.1, 2 Although several genes are thought to cause this disease the exact genetic cause remains unknown, and most cases of CVID are sporadic.2, 3 The European Society for Immunodeficiencies (ESID) and the Pan-American Group for Immune Deficiency (PAGID) published the diagnostic criteria in 1999. They defined CVID as a patient presenting with low IgG, IgA, and/or IgM levels, onset of immunodeficiency at more than 2 years of age, and impaired antibody response, with the exclusion of other causes of hypogammaglobinemia such as drugs, infectious diseases, or malignancy.⁴ The International Consensus on Common Variable Immunodeficiency Disorders (ICON) offered new criteria for the diagnosis of CVID in 2015,³ and ESID recently revised its criteria.⁵ CVID can be seen at any age from early childhood, but it is considered a diagnosis of exclusion and is difficult to distinguish from other immunodeficiencies; therefore, diagnosis should be delayed until the patient reaches at least 4 years of age.1, 3

The clinical and immunological spectrum of CVID displays great diversity. Although patients usually present with recurrent respiratory tract infections, many clinical problems including chronic lung disease, gastrointestinal disease, autoimmunity, lymphoproliferative disorders, and malignancy are commonly seen, which cause frequent hospitalization in this patient group.3, 6, 7 Early diagnosis and treatment are important. The general treatment is immunoglobulin (Ig) replacement therapy, which reduces serious bacterial infections. Along with Ig therapy, any infections that arise must be treated aggressively with antibiotics.⁸ The clinician must watch carefully for new symptoms and should monitor the patient regularly for complications such as autoimmunity, malignancy, or gastrointestinal problems.⁸

The aim of the study was to determine the clinical and immunological features of Turkish patients with CVID referred to Istanbul Cerrahpasa Medical School Pediatric Immunology Center over a period of 20 years.