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.

Keywords: Primary antibody deficiency, Recurrent respiratory tract infections, Complications, Immunoglobulin replacement, Adults, Early diagnosis

Core Tip: Common variable immunodeficiency has to be considered in adults with recurrent respiratory tract infections, bronchiectasis, cytopenia, generalized lymphadenopathy, sarcoid-like symptoms, colitis in whom other conditions were excluded. Low calculated globulin, which is the difference between total protein and albumin levels, suggests hypogammaglobulinemia. Patient with common variable immunodeficiency are referred for commencing replacement immunoglobulin therapy, which should be continued regularly throughout life. It can be administered intravenously, subcutaneously and via the hyaluronidase-facilitated subcutaneous route. One must bear in mind that in patients with hypogammaglo-bulinemia and those treated with polyclonal immunoglobulin G products, serological tests based on determination of antibodies are unreliable.