Undiagnosed Chronic Granulomatous Disease, Burkholderia cepacia complex Pneumonia, and Acquired Hemophagocytic Lymphohistiocytosis: A Deadly Association
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. 1. Introduction Chronic granulomatous disease (CGD) is an inherited disorder of the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which results in impaired production of reactive oxygen species and subsequent compromised antimicrobial defenses [1, 2]. CGD accounts for 1.1% of cases of primary immunodeficiency and the prevalence has been estimated to be close to 1/300000 [3]. There are different forms of CGD caused by different mutations in the genes coding for the NADPH oxidase protein complex. However, the majority of cases encountered in clinical practice followed an X-linked pattern of inheritance [3] and originated from a defect of gp1-phox gene, either the gene expression or the protein function. This type of CGD is more severe, and diagnosis is usually made within the first year of life because of recurrent infections [3]. The autosomic recessive form of CGD involves genes that encode p22-phox, p67-phox, and p47-phox. This form is less severe, and consequently, the diagnosis is usually made during the second decade of life. One of the most frequent germs encountered in CGD patients is Burkholderia cepacia complex (Bcc). This motile Gram negative bacillus is involved in at least 3% to 7% of pneumonia and in 18% of deaths in CGD [3, 4]. The treatment
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