Clinically, XLR-CGD is prevalent in men and is carried by women . Recurrent infections are common in patients with CGD. Moreover, CGD may present with granulomas or inflammatory disorders. The infections commonly affect the lungs, skin, lymph nodes, gastrointestinal tract and bone marrow. The common causative pathogens are catalase-positive bacteria and fungi, such as Staphylococcus aureus, Burkholderia cepacia, Serratia marcescens, Aspergillus fumigatus, and Candida albicans .
In the present case, the patient did not show prominent digestive tract symptoms. However, he presented with fever, intestinal wall thickening, and ascites. Culture of the ascetic fluid showed that B. Contaminans was positive. The most commonly affected organs in patients with CGD include the gastrointestinal tract (nearly 100%), with inflammatory bowel disease (IBD) accounting for 33% of all cases. Inflammatory and autoimmune complications with the X-linked inheritance pattern are twice as high as those in patients with AR-CGD . In the present patient, invasive enteroscopy was not performed due to the rapid resolution of symptoms. Persistent intestinal wall thickening, elevated levels of CRP, IgG, platelet count, and response to glucocorticoid therapy confirmed the presence of hyperinflammation. In addition, the chest CT showed concealed pneumonia. Hydrocele in the right testes which may have been caused by unclosed sheath process resolved after the initial treatment for about ten days .
Burkholderia sensu stricto contains the Burkholderia cepacia complex (Bcc) and Burkholderia pseudomallei group. Both B. contaminated and B. cepacia belong to the Bcc. It is a group of gram-negative bacteria, which are common in the environment, and cause opportunistic infections. The Bcc is mostly causing pneumonia in patients with CGD and shows resistance to multiple drugs. B. contaminated is sensitive to trimethoprim-sulfamethoxazole, chloramphenicol, minocycline, ceftazidime, piperacillin/tazobactam and carbapenem . It was first reported in patients with cystic fibrosis (CF) and associated with various infections, especially necrotizing pneumonia and the worsening of pulmonary function. Since then, it has been detected in patients undergoing cataract surgery and biliary tract infections, presented as endophthalmitis and sepsis respectively.It is mostly caused by contact with medical devices or contaminated aqueous solutions including nebulized medications, ultrasound gel, nasal spray, lipid emulsion, and hospital water, which may be responsible for hospital outbreaks [9,10,11,12]. BCG infections occur frequently in patients with CGD and the patient was given prophylactic anti-tuberculosis treatment (rifampicin).
Due to unusual germs and site of the patient, NADPH activity was tested, and showed a profound decrease in NADPH activity. Further, genome sequencing revealed a de novo nonsense mutation in the coding region of exon 6 of CYBB. This mutation shifts tyrosine to a premature termination codon at 201th amino acid (c. 603C > A), resulting in abnormal expression of gp91phox, and its domain is located at the N-terminal. According to recent research, about 61% of mutations in CYBB gene occur in the N-terminal domain, mostly fragment deletions and splicing errors [13, 14].
The survival of patients with CGD is closely influenced by production of residual reactive oxygen intermediates (ROIs). Compared with children with AR-CGD, those with XLR-CGD have an earlier disease onset and more severe disease leading to higher mortality. Missense mutations in CYBB can decrease levels of superoxide or gp91phox expression. In contrast, nonsense mutations inhibit the production of superoxide and protein expression, thereby decreasing the survival rate [15, 16].
Anti-infective therapy can significantly improve the quality of life and survival rate of CGD patients. Subcutaneous injection of interferon-γ decreases the risk of infection, especially in patients who acquire infections while on prophylactic antibiotics and those infected with tuberculosis . Patients with CGD have excessively high levels of cytokines, such as TNF-α, IL-1, IL-8, which predispose them to hemophagocytic lymphohistiocytosis (HLH) when infected. The incidence of inflammatory complications in patients with XLR-CGD is twice as high as that in patients with AR-CGD [6, 18]. Appropriate anti-inflammatory agents, mainly corticosteroids, can significantly improve the prognosis of patients with CGD, and do not appear to increase the bacterial infection risk . The recommended initial dose of prednisone is 1 mg/kg daily and to be given for an average of 2-3 weeks before being tapered over several months . Biological disease modifying antirheumatic drug (bDMARDs), such as anti-TNF-a monoclonal antibodies, recombinant IL-1receptor-targeted antagonist and IL-23 antagonist have been used, but there are increased risks of infection. HSCT remains the best curative option for CGD. The major problem is the risk of infection and graft-versus-host disease (GVHD). Lower risk patients may be best treated by HSCT. For high-risk patients and patients who have no well-matched donor, gene therapy may be considered. Although preliminary results using lentiviral vectors are fairly encouraging, gene therapy still faces many challenges [3, 20].