Risk Factors and Clinical Significance of Lymphopenia in Survivors of the Fontan Procedure for Single-Ventricle Congenital Cardiac Disease

Abstract

Background: Congenital cardiac anomalies are associated with immunologic perturbations. Surgical thymectomy, thoracic duct manipulation, and protein- losing enteropathy (PLE), a condition related to stressed Fontan hemodynamics, presumably contribute to low peripheral absolute lymphocyte counts (ALCs) and quantitative immunoglobulins. Clinical significance of lymphopenia and hypogammaglobulinemia in single-ventricle survivors requires additional study.

Objective: Although immunologic laboratory anomalies are common in this population, we hypothesize that clinically significant immunodeficiency requiring intervention is rarely required.

Methods: A retrospective chart review of the immunologic parameters of patients enrolled in the Single Ventricle Survivorship Program (SVSP) at the Children's Hospital of Philadelphia was performed.

Results: The age range of the 178 SVSP patients was 3 to 26 years, with a median of 10.8 years. Most of the SVSP patients had some degree of lymphopenia. In the non-PLE group, the range of ALCs varied from 530 to 5322 cells/μL, with 17 patients without PLE maintaining an ALC of less than 1000 cells/μL. Among those with PLE, the median ALC and the IgG level were lower (672 cells/μL and 200 mg/dL, respectively) than in those without (1610 cells/μL and 868 mg/dL, respectively). Despite lymphopenia in the majority, few were severely clinically affected: 24% had delayed clearance of cutaneous viral infections, 63% had atopy, and 1 died of EBV-associated Hodgkin lymphoma. Immunoglobulin replacement was clinically indicated for 3 patients, 1 of whom had common variable immunodeficiency. Four patients with normal splenic function were treated with daily antibiotic prophylaxis.

Conclusions: Patients with repaired single-ventricle physiology often demonstrate T-cell lymphopenia and hypogammaglobulinemia. A significant portion of patients without PLE also have lymphopenia. The most common clinical manifestation was delayed clearance of cutaneous viral infections, but significant systemic opportunistic infections were not seen despite laboratory abnormalities and lack of antimicrobial prophylaxis.

Keywords: Fontan; Hypogammaglobulinemia; Protein-losing enteropathy (PLE); Secondary immunodeficiency; Single ventricle; T-cell lymphopenia; Warts.