Current challenges in secondary immunodeficiency

This review is proposing a definition of secondary immunodeficiency (SID), by substantiating its role within the framework of multimorbidities, and evaluating the clinical consequences of multimorbidity in presence of SID conditions. The article summarizes the limited available epidemiological data on the prevalence of SID, analyzes the most common risk factors and causes of immunodeficiency, and highlights the expanding spectrum of these factors in view of recent advances in understanding disease pathogenesis and pharmacodynamics of modern drugs that may adversely affect immune cells and mediators. A structured clinical pathway for medical management is proposed, starting with assessment of risk factors and early clinical manifestations of SID, in particular, severe and recurrent infections as key clinical markers, and resulting in the diagnosis of immunodeficiency. These recommendations are based on expert consensus statements developed by multidisciplinary teams of clinicians and immunologists. The review also presents a detailed diagnostic algorithm for patients with suspected secondary immunodeficiency, including comprehensive medical history taking and clinical assessment to guide appropriate laboratory evaluation, including immunological testing. It is emphasized that normal immune parameters do not exclude the diagnosis of SID in patients with severe or recurrent infections. Approaches to differentiated anti-infection prophylaxis across various risk groups are discussed, along with the main therapeutic strategies for SID, including vaccination and immunoglobulin therapy. At the same time, the limited evidence regarding the efficacy and safety of vaccines and immunoglobulins in the treatment of SID is highlighted. The article concludes that optimal management of patients with SID requires a multidisciplinary clinical team, with mandatory involvement of a clinical immunologist.