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.
Keywords: chronic granulomatous disease; fungemia; hemophagocytic lymphohistiocytosis; immunocompromised host; immunomodulation.
Copyright © 2014 by the American Academy of Pediatrics.