Secondary Combined Immunodeficiency in Pediatric Patients after the Fontan Operation: Three Case Reports

Abstract

The Fontan operation or total cavopulmonal connection (TCPC) is a palliative surgical correction of rare and complex inborn cardiac malformations that are characterized by univentricular circulation. Protein-losing enteropathy (PLE) develops in 4-13% of patients after the Fontan procedure. Fontan-related PLE leads to secondary combined immunodeficiency marked by hypogammaglobulinemia and predominantly CD4⁺ lymphocytopenia. Here, we present 3 case reports of patients with secondary immunodeficiency after the Fontan operation. The severity of hypogammaglobulinemia correlated with the nature of the infectious complications; however, clinical manifestations of T cell deficiency such as severe viral or opportunistic infections were not observed. The clinical consequences of the secondary combined immunodeficiency were modified by immunoglobulin replacement treatment and antibiotic prophylaxis. Heart transplantation led to the resolution of PLE signs and the restitution of IgG levels in 1 transplanted patient. Our experience shows that the immunological follow-up was delayed in all 3 patients. We suggest that all patients should be followed regularly by a clinical immunologist after the Fontan surgery.

The Expanding Field of Secondary Antibody Deficiency: Causes, Diagnosis, and Management

“…Common causes of secondary antibody deficiency (26), (5), (251), (255), (256), (242), (6), (144), (7), (165), (70), (242), (18), (168), (244), (134), (141), (135), (139), (133), (155), (245), (147), (138), (38), (162), (124), (163), (246), (174), (233), (253), (257), (247), (252), (249), (250), (10), (254). Reproduced with the permission of the copyright holder John Wiley & Sons Inc (5).…”

Practical guidance for the diagnosis and management of secondary hypogammaglobulinemia: A Work Group Report of the AAAAI Primary Immunodeficiency and Altered Immune Response Committees

“…41 Studies of IgG-RT in SHG have been mostly performed with IVIG (Table VI). There are potential benefits to SCIG including better tolerance of infusions and reduced protein loss, and reports of SCIG used for SHG associated with hematologic malignancy, 42,43 SOT, 44,45 and protein-losing conditions [46][47][48][49] suggest that it is well tolerated and effective at increasing IgG levels in these cases. In the absence of additional data, the decision to initiate IVIG or SCIG needs to involve shared decision making with the patient.…”

“…334 PLE is estimated to occur weeks to years after the Fontan operation in 3% to 18% of patients. 48,[336][337][338][339][340] Patients who have undergone a Fontan procedure and related surgeries demonstrate variable degrees of T-cell lymphopenia, SHG, and decreased or negative specific vaccine titers. 48,[331][332][333]341,342 The use of immunomodulators such as corticosteroids may increase the risk of infection in these patients.…”

“…SCIG has led to clinical and IgG level improvement in a patient in whom IVIG had previously failed to provide adequate IgG levels 47 and in 4 patients with SHG post-Fontan. 48,49…”

When to initiate immunoglobulin replacement therapy (IGRT) in antibody deficiency: a practical approach

“…The use of IGRT in protein‐losing states is problematic and, again, antibiotic prophylaxis would be indicated ahead of IGRT. If IGRT is required, the pharmacokinetics of the subcutaneous route may be preferable, as it avoids the peak levels and longer cycle duration of intravenous Ig (IVIg) . This would reduce infections with improved overall antibody levels afforded by more frequent dosing and limiting the higher rates of loss associated with the IgG peak levels following IVIg.…”