From infections to autoimmunity: Diagnostic challenges in common variable immunodeficiency

Abstract

Common variable immunodeficiency (CVID) is the most common clinically significant primary antibody deficiency diagnosed in adults. The early symptoms are not specific. They include common infections, mainly of the respiratory tract, caused by typical microorganisms, so cases can be missed in primary care. In the majority of patients increased susceptibility to infections coexists with signs or symptoms of autoimmunity, inflammation or polyclonal lymphoproliferation, which can divert diagnosis from immune deficiency. The overall incidence of malignancy is increased in CVID and certain cancers are significantly more common. Lymphomas and gastric carcinoma are the most frequently reported malignancies in CVID, so a high index of suspicion is recommended. Diagnostic delay in CVID is seen worldwide. The main goal of this paper is to increase the awareness about CVID among health care professionals. We aim to present features which can be helpful in CVID diagnosis in order to shorten the “latency” of proper management of CVID patients. We review clinical symptoms, complications and laboratory abnormalities of CVID. Immunoglobulin replacement therapy is regarded as the cornerstone of pharmacological intervention. New modes of Ig application, mainly subcutaneously and via the hyaluronidase-facilitated subcutaneous route, help to adjust therapy to patients’ needs and preferences. Still there remain unmet needs. It remains to be seen whether CVID complications can be avoided by earlier diagnosis, treatment and thorough monitoring in the context of increased risk of malignancy. Development of patient tailored protocols depending on the clinical phenotype and risk factors might be more appropriate. The most important consideration is to diagnose suspected cases and stratify patients in a precise and timely way. Work is needed to define features predictive of unfavorable prognosis.

Patients with Common Variable Immunodeficiency Complicated by Autoimmune Phenomena Have Lymphopenia and Reduced Treg, Th17, and NK Cells

“…Common variable immunodeficiency (CVID) is the most common symptomatic primary antibody deficiency in adults. Most patients suffer from recurring respiratory tract infections; however, paradoxical autoimmunity, both systemic and organ related, is a secondary manifestation of CVID and affects 20–40% of cases [ 1 ]. Patients with a complicated CVID phenotype have the longest diagnostic delay, especially if autoimmune phenomena are the first manifestations of primary immunodeficiency [ 2 ].…”

Neurologic Manifestations of Common Variable Immunodeficiency

“…Many people diagnosed with CVID experience a significant delay in diagnosis of between 5 and 10 years 33 When a diagnosis is obtained, often in a subspecialty immunology clinic, the focus of management is largely on preventing and treating infection(s) and secondarily on vigilance diagnosing associated autoimmune diseases, lymphoproliferative disorders, malignancy screening, and gastrointestinal complications. 34 Other studies have shown that delayed diagnosis was correlated with some health-related quality of life (HRQL) dimensions in pediatric and adult patients, suggesting that early diagnosis and treatment may improve some of these HRQL parameters.…”

Uncommon presentations of common variable immunodeficiency

“…CVID is frequently associated with diverse infections caused by numerous microbes. Table 1 highlights the various respiratory infections and their aetiologies that have been reported with CVID, the most common being with encapsulated organisms like Haemophilus influenzae , Streptococcus pneumoniae , Neisseria meningitidis along with Enterovirus 1–17…”