Cytomegalovirus in primary immunodeficiency

Abstract

Purpose of reviewCytomegalovirus (CMV) infection and disease are well described in the setting of secondary immunodeficiency. Less is known about CMV in the context of primary immunodeficiencies (PIDs), where inborn errors in one or more arms of the immune system result in variable degrees of CMV susceptibility. Recent findingsPID presents unique challenges in the diagnosis and management of CMV disease. The clinical presentation of CMV in PID is often severe, accelerated by underlying immune dysregulation and iatrogenic immunosuppression. Here we describe the clinical significance of CMV infection in PID, the key components of immune defence against CMV and how these are affected in specific PIDs. CMV disease is under-recognized as a complication of common variable immunodeficiency (CVID). High rates of CMV end-organ disease, mortality, development of CMV resistance and prolonged antiviral use have been observed in individuals with CVID.

Case Report: Cytomegalovirus Disease Is an Under-Recognized Contributor to Morbidity and Mortality in Common Variable Immunodeficiency

“…Rates of inflammatory disease in our patients with CMV disease (100%) were higher than the frequency reported in the pooled literature (77%) (9). This could be considered support for the hypothesis that an unrestrained T-cell response to CMV drives end-organ inflammation in CVID, even in the absence of detectable CMV viraemia or diagnostic histology.…”

“…The most striking clinical characteristics of our CVID + /CMV + cohort were the high prevalence of monogenic CVID (66.7%, 4/6) and mortality rates (66.7%, 4/6 in 5 years). It is apparent from the case literature that treatment of CMV is a burdensome and often failed endeavor ( 9 ), but the potential impact of CMV disease on life expectancy in CVID has never been so starkly presented before.…”

“…CMV disease is generally defined as the presence of tissue-invasive CMV associated with an appropriate clinical syndrome ( 7 , 9 ). It occurs when viral replication is reactivated, and is commonly encountered in secondary immunodeficiencies, for example, following haematopoietic stem cell transplantation (HSCT), or in the setting of acquired immunodeficiency syndrome.…”

“…It occurs when viral replication is reactivated, and is commonly encountered in secondary immunodeficiencies, for example, following haematopoietic stem cell transplantation (HSCT), or in the setting of acquired immunodeficiency syndrome. It was recently reported that CMV disease in CVID is relatively common and can result in fatal clinical outcomes ( 9 ). However, knowledge of CMV’s impact on the immune response in the context of CVID-associated immunodeficiency is limited.…”

Clinical Characteristics and Outcomes of Primary Immunodeficiency Diseases Complicated with Autoimmune disorders: Experience from a Single Tertiary Center

“…In this cohort, all PID patients experienced ≥ three episodes of infections. As for infection sites, respiratory tract infection with symptoms of recurrent cough and expectoration were most recorded in these patients (85, 35.3%); gastrointestinal infection (43, 17.8%), sinusitis/otitis (27, 11.2%), intracranial infection (12, 5.0%), skin infection (12, 5.0%) and urinary tract infection(11,4.6%) were also frequently reported. Typical pathogens included Streptococcus pneumoniae (41, 17.0%) and Haemophilus in uenzae (29, 12.0%).…”