Valentine Gregory, Thomas Tessy A, Nguyen Trung, Lai Yi-Chen
Section of Pediatric Critical Care Medicine, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
Section of Pediatric Critical Care Medicine, Department of Pediatrics, Baylor College of Medicine, Houston, Texas
Pediatrics. 2014 Dec;134(6):e1727-30. doi: 10.1542/peds.2014-2175.
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.
慢性肉芽肿病(CGD)是一种原发性免疫缺陷病,其特征为反复感染和炎症反应失调。在CGD患者中已观察到感染引发的噬血细胞性淋巴组织细胞增生症(HLH),表现为病理性的炎症反应亢进。然而,此前尚无HLH作为首发表现随后被诊断为CGD的报道。此外,HLH的主要治疗策略侧重于免疫抑制疗法,这限制了免疫介导的组织损伤。对于存在免疫缺陷的患者,这种治疗策略可能会使病情恶化。本文讨论了一名8周大的西班牙裔男性,他因不明原因发热就诊。初始诊断评估显示存在病理性炎症反应亢进,符合HLH-2004诊断标准,但未发现明确的感染病因。于是启动了免疫抑制治疗,随后患者出现播散性念珠菌败血症休克及败血症诱发的多系统器官衰竭。进一步评估最终确诊为CGD。我们转而采用免疫增强策略,输注粒细胞和免疫球蛋白,并加强抗真菌治疗。这些干预措施最终使真菌感染得以清除,炎症反应亢进状态得到缓解。该病例是首例报道的以HLH为首发表现随后诊断为CGD的病例。它提醒我们,免疫缺陷和炎症性疾病可能都具有病理性炎症反应亢进的特征,并凸显了临床医生在未解决感染的情况下治疗HLH时所面临的难题。在本病例报告中,我们证明免疫增强疗法可能有助于控制和清除感染,从而反常地减轻病理性炎症反应亢进。