Chronic Granulomatous Disease Presenting as Hemophagocytic Lymphohistiocytosis: A Case Report

Abstract

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by recurrent infections and a dysregulated inflammatory response. Infection-triggered hemophagocytic lymphohistiocytosis (HLH), which manifests itself as pathologic hyperactive inflammation, has been observed in subjects with CGD. However, there have been no reports of HLH as the initial presentation with subsequent diagnosis of CGD. Furthermore, the primary therapeutic strategy for HLH focuses on immunosuppressive therapies, which limits immune-mediated tissue damage. With immunodeficiency, this therapeutic strategy may worsen the outcome. This article discusses an 8-week-old Hispanic male who presented with fever of unknown origin. The initial diagnostic evaluation demonstrated pathologic hyperactive inflammation, meeting the HLH-2004 diagnostic criteria without an identified infectious etiology. Immunosuppressive therapy was initiated, with subsequent disseminated candida septic shock and sepsis-induced multisystem organ failure. Additional evaluations ultimately established the diagnosis of CGD. We transitioned to an immune-enhancing strategy with granulocyte and immunoglobulin infusions, and intensified antifungal therapies. These interventions ultimately led to the clearance of the fungal infection and the resolution of the hyperactive inflammatory state. This case represents the first reported case of HLH as the presenting finding leading to the subsequent diagnosis of CGD. It serves as a reminder that both immunodeficiency and inflammatory disorders may share features of pathologic hyperactive inflammation and highlights the conundrum that clinicians face when treating HLH in the setting of an unresolved infection. In this case report, we demonstrate that immune-enhancing therapies may aid in the control and the clearance of the infection, thus paradoxically decreasing the pathologic hyperactive inflammatory response.

Hemophagocytic lymphohistiocytosis resulting from a cytokine storm triggered by septicemia in a child with chronic granuloma disease: a case report and literature review

“…Álvarez-Cardona also reported two cases of CGD complicated by MAS that were successfully treated with IVIG [7]. For such patients, using antibiotic drugs alone cannot achieve a good response [9]. Our patient was not diagnosed with CGD at admission, but he was young and had repeated infections after birth, suggesting that he might have a congenital immune deficiency.…”

“…Repeated infections result in an increased risk for developing HLH. Infection-associated hemophagocytic syndrome (IASH) with CGD has been observed in eight children and two adults [5][6][7][8][9]. We report a case of CGD with repeated Salmonella septicemia complicated with HLH, and the CGD mutation identified has not been reported.…”

Newborn Screening for Primary Immunodeficiencies: The Gaps, Challenges, and Outlook for Developing Countries

“…Hence, genetic testing is indicated in neonates with unexplained hydrops. Hepatosplenomegaly in the neonatal period has been described in hemophagocytic lymphohistiocytosis, and CGD (59). As confirmation of the importance of clinical identification of PID patients, the survival of patients diagnosed clinically was identical to those diagnosed by NBS, positive family history, or both (60).…”

Macrophage activation syndrome/haemophagocytic lymphohistiocytosis secondary toBurkholderia cepaciacomplex septicaemia in an elderly female carrier of X-linked chronic granulomatous disease with extreme lyonisation: ‘cepacia syndrome’ revisited

“…MAS/HLH, although well recognised as a complication of CGD, is rare. There have been 14 cases to date describing MAS/HLH in CGD patients,7 18–21 with four of them appearing to be triggered by a member of the B. cepacia complex. Case reports of female X-linked carriers with a mutated CYBB gene, who have become immunodeficient through skewed lyonisation, have also previously been described,6 22–24 although our case is the first documented case of an elderly female carrier of X-linked CGD with profound skewing of lyonisation resulting in susceptibility to B. cepacia with triggering of MAS/HLH.…”