Pulmonary Manifestations of Congenital Defects of Phagocytes

The phagocytic system is an indispensable part of the immune defense mechanism and innate immune system. Pulmonary manifestations could be either ambiguous or misleading. The most common involved organ in chronic granulomatous deficiency (CGD) is the lung, which manifests with infectious and non-infectious (granuloma and fibrosis) complications. Myeloperoxidase (MPO)-deficient individuals are mostly asymptomatic; however, invasive Candida (IC) may present as candidemia, disseminated infection, and pneumonia. Neutrophil-specific granule deficiency pulmonary manifestations are recurrent pneumonias and lung abscess mostly due to Staphylococcus aureus and Pseudomonas aeruginosa. In leukocyte adhesion deficiency (LAD), involvement of the skin and mucus membranes is a predominant clinical feature and then recurrent pulmonary infections. In RAC-2 deficiency, pulmonary involvement although uncommon includes recurrent sinopulmonary infections, pneumonia, and bronchiectasis. In congenital neutropenia (CN), the child might begin to have fevers associated with respiratory symptoms of pneumonia. ELANE (neutrophil elastase) mutations are the most frequent known cause of congenital neutropenia which is characterized by oropharyngeal inflammation. G6PC3 deficiency and its severe form called Dursun syndrome are characterized by a triad of familial primary pulmonary hypertension (PPH), leukopenia, and atrial septal defects. Cyclic neutropenia is characterized by oscillating numbers of blood neutrophils. Pulmonary manifestations are upper respiratory infections (sinusitis and otitis media), pneumonia, and bronchitis. In Shwachman-Diamond syndrome (SDS), pulmonary manifestations are recurrent bronchopulmonary bacterial, viral, and fungal opportunistic infections and recurrent otitis media. Cohen syndrome is associated with laryngeal dysfunction and laryngomalacia to stenosis and vocal cord paralysis. Poikiloderma often accompanies severe neutropenia and bronchiectasis, lung abscesses, and lung granulomas. In other phagocytic deficiencies, including b-actin, aggressive periodontitis, Papillon-Lefevre syndrome, Barth syndrome, and glycogen storage disease Ib, no pulmonary manifestations have been reported.