Undiagnosed Chronic Granulomatous Disease,Burkholderia cepacia complexPneumonia, and Acquired Hemophagocytic Lymphohistiocytosis: A Deadly Association

Abstract

Background. Chronic granulomatous disease is a rare inherited disorder of the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The clinical course of the disease is marked by recurrent infections, including Burkholderia cepacia complex infection. Case Report. Here we report the case of a 21-year-old male hospitalized for a Burkholderia cepacia complex pneumonia. Despite the broad spectrum antibiotic treatment, fever continued and patient's condition worsened. Anemia and thrombocytopenia developed together with hypofibrinogenemia. The patient died of multiple organ dysfunction 17 days after his admission. Autopsy revealed hemophagocytosis, suggesting the diagnosis of acquired hemophagocytic lymphohistiocytosis. DNA analysis showed a deletion in the p47phox gene, confirming the diagnosis of autosomal recessive chronic granulomatous disease. Discussion. In addition to chronic granulomatous disease, recent findings have demonstrated that Burkholderia cepacia complex can decrease activity of the NADPH oxidase. Interestingly, hemophagocytic lymphohistiocytosis is characterized by an impaired function of the T-cell mediated inflammation which is partly regulated by the NADPH oxidase. Physicians should therefore pay particular attention to this deadly association.

Chronic Granulomatous Disease Presenting as Hemophagocytic Lymphohistiocytosis: A Case Report

“…Although dysregulated inflammation can manifest as sterile granulomas and discoid lupus in patients with CGD, all reported cases of HLHwithoverwhelming pathologic immune activation occur in the setting of persistent infection [4][5][6][7][8][9] suggesting that impaired pathogen killing underlies the pathologic hyperactive inflammation. Interestingly, all patients who received intravenous immunoglobulin and pathogen-specific therapies survived, 4,5,7,8 while the reported deaths occurred in patients who received either inadequate pathogen-specific therapy or immunosuppressive therapies for HLH.…”

“…Interestingly, all patients who received intravenous immunoglobulin and pathogen-specific therapies survived, 4,5,7,8 while the reported deaths occurred in patients who received either inadequate pathogen-specific therapy or immunosuppressive therapies for HLH. 6,9 Therefore, perhaps in patients with CGD who also have infection-triggered HLH, greater focus on eliminating the infection by immune-enhancing strategies may paradoxically decrease the hyperactive inflammatory response and improve the clinical outcome. We modulated our therapeutic goals from immunosuppression to immune enhancement and were successful in achieving control of the fungal infection without exacerbating the inflammatory response.…”

“…Accordingly, infection-triggered hemophagocytic lymphohistiocytosis (HLH) has been reported in patients with CGD with concurrent infections. [4][5][6][7][8][9] However, there have been no reports of HLH as the presenting clinical finding leading to the diagnosis of CGD.…”

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

“…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.…”